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1.
In the frog glossopharyngeal nerve, single water fibers respondto low CaCl2 (12 mM) and relatively high MgCl2 (100 mM).In the present study, it was found that stimulation by a mixtureof low CaCl2 and relatively high MgCl2 led to a small response.This suggests that the Ca+ response is inhibited by the presenceof Mg2+ and the Mg2+ response is inhibited by the presence ofCa2+. Hence, it is suggested that there are different receptorsites for divalent cations in single water fibers of the frogglossopharyngeal nerve, a calcium receptor site (XCa) responsiblefor the Ca2+ response and a magnesium receptor site (XMg) responsiblefor the Mg2+ response. It has been reported that Mg2+ inhibitsthe Ca2+ response by competing with Ca2+ for XCa (Kitada andShimada, 1980). In the present study, the inhibition of theMg2+ response by Ca2+ was examined quantitatively under theassumption that the magnitude of the neural response is proportionalto the amount of MgXMg complex minus a constant (the thresholdconcentration of the MgXMg complex). The results obtained indicatethat Ca2+ competes with Mg2+ for XMg. The apparent dissociationconstants for MgXMg complex and CaXMg complex, which were obtainedfrom the present study, were 8.0 x 102 M and 7.2 x 104M, respectively. Thus, competition between Ca+ and Mg2+ forthe distinct receptor sites involved in taste reception wasdemonstrated by the results described in this paper. Since thedivalent cations do not always bring about activation of tastereceptors, the responses to salts in the frog glossopharyngealnerve cannot be explained in terms of changes in the surfacepotential outside the taste cells. The present results suggestthat there exist multiple specific receptor sites for cationsinvolved in salt taste responses, and only the binding of eachseparate cation to its appropriate receptor sites leads to activationof the receptor and the initiation of impulses in sensory nerveendings. 相似文献
2.
Decrease in rat taste receptor cell intracellular pH is the proximate stimulus in sour taste transduction 总被引:10,自引:0,他引:10
Lyall V Alam RI Phan DQ Ereso GL Phan TH Malik SA Montrose MH Chu S Heck GL Feldman GM DeSimone JA 《American journal of physiology. Cell physiology》2001,281(3):C1005-C1013
Taste receptor cells (TRCs)respond to acid stimulation, initiating perception of sour taste.Paradoxically, the pH of weak acidic stimuli correlates poorly with theperception of their sourness. A fundamental issue surrounding sourtaste reception is the identity of the sour stimulus. We tested thehypothesis that acids induce sour taste perception by penetratingplasma membranes as H+ ions or as undissociated moleculesand decreasing the intracellular pH (pHi) of TRCs. Our datasuggest that taste nerve responses to weak acids (acetic acid andCO2) are independent of stimulus pH but strongly correlatewith the intracellular acidification of polarized TRCs. Taste nerveresponses to CO2 were voltage sensitive and were blockedwith MK-417, a specific blocker of carbonic anhydrase. Strong acids(HCl) decrease pHi in a subset of TRCs that contain apathway for H+ entry. Both the apical membrane and theparacellular shunt pathway restrict H+ entry such that alarge decrease in apical pH is translated into a relatively smallchange in TRC pHi within the physiological range. Weconclude that a decrease in TRC pHi is the proximate stimulus in rat sour taste transduction. 相似文献
3.
In single water-sensitive fibers (water fibers) of the frogglossopharyngeal nerve, application of a solution of 500 mMcholine Cl to the tongue elicited responses of varying magnitude.Some water fibers (plain choline-insensitive water fibers) barelyresponded to the solution, while some water fibers (plain choline-sensitivewater fibers) exhibited a considerable response to this solution.NiCl2. which is barely effective in producing neural responseat concentrations below 5 mM, induced the response of plaincholine-insensitrve water fibers to choline+ ions. It was confirmed,in a collision test, that the Ni2+-induced responses to choline+ions were derived from water fibers. However, NiCl2 did notaffect the magnitude of me response generated by choline+ ionsin plain choline-sensitive water fibers. The concentration-responsecurve for choline Cl in the presence of 1 mM NiCl2 for plaincholine-insensitive water fibers was similar to the curves obtainedin the absence of NiCl2 for plain choline-sensitive water fibers.Other organic salts, such as tris(hydroxymethyl)arrdnomethane-HCl,triethanotamine-HCl and tetraethylammonium Cl, elicited no responseor only a very small response from water fibers, and NiCl2 didnot affect these responses. It is suggested that there existsa choline receptor for the response to choline+ ions in theapical membrane of frog taste cells and that Ni2+ ions exposethe sites of such choline receptors, which are deeply embeddedin the receptor membrane, to the outside medium. The effectof Ni2+ ions results in an increase in the number of the cholinereceptor sites available for binding of choline+ ions. The rankorder of effectiveness of transition metal ions in elicitingthe appearance or enhancement of the response to choline Clwas Ni2+ > Co2+ > Mn2+. Mg2+ ions had no effect on theresponse to choline+ ions. A similar rank order was previouslyobtained in enhancement of the responses to Ca2+, Mg2+ and Na2+ions (Kitada, 1994a). It seems likely that the mechanism forenhancement or elicitation of the response to choline+ ionsby the transition metal ions has features in common with thatfor enhancement of the responses to Ca2+, Mg2+ and Na+ ions. 相似文献
4.
NiCl2 induces a response to cboline Cl and enhances the responseto CaCl2 in water-sensitiv fibers (water fibers) of the frogglossopharyngeal nerve. The Ni2+-induced choline+ response wasinhibited by Ca2+ ions and, conversely, the enhanced Ca2+ responseby Ni2+ ions was inhibited by choline+ ions. Hence, there existsa mutual antagonism between Ca2+ and choline+ ions. In the presentstudy, the inhibition of the Ni2+-induced choline+ responseby Ca2+ ions was investigated quantitatively. The assumptionwas made that receptors for choline (XCh) exist and that bindingof a choline+ ion to XCh, brings about a neural response. Itwas further assumed that the magnitude of the neural responseis proportional to the amount of choline-XCh, complex minussome constant (the threshold concentration of the choline-XCh,complex). The results from analysis of double-reciprocal plotwere consistent with the hypothesis that Ca2+ ions compete withcholine+ ions for XCh,. The dissociation constants for the choline-XCh,complex and the CaXCh, complex were obtained to be 0.6 M and7.4 x 10-5 M, respectively. This result indicates that the affinitiesof XCh, for choline+ and Ca2+ ions are very different. Furthermore,Mg2+ ions did not affect the Ni2+-induced choline+ response,an indication that the affinity of XCh, is not charge-specific,but is chemically specific. The identification of a competitiveinhibitor of the choline+ response provide* evidence for existenceof a choline-specific receptor at the surface of taste cellsthat are innervated by the water fibers of the frog glossopharyngealnerve. Differences between the features of the response to cholineCl in the chorda tympani nerve of the rat and those in the frogglossopharyngeal nerve are discussed. 相似文献
5.
Fibers of the frog glossopharyngeal nerve (water fibers) thatare sensitive to water also respond to CaCl2, MgCl2 and NaCl.In the present study, interaction among cations (Ca2+, Mg2+and Na+) on taste cell membrane in frogs was studied using transitionmetals (NiCl2, CoCl2 and MnCl2), which themselves are barelyeffective in producing neural response at concentrations below5 mM. Unitary discharges from single water fibers were recordedfrom fungiform papillae with suction electrode. Transition metalions (0.055.0 mM) had exclusively enhancing effects onthe responses to 50 mM Ca2+, 100 mM Mg2+ and 500 mM Na+. Theeffects of transition metal ions were always reversible. Therank order of effectiveness of transition metals at 1 mM inthe enhancement of the responses to 50 mM CaCl2, 100 mM MgCl2and 500 mM NaCl was NiCl2 > CoCl2 > MnCl2. The concentrationof transition metal ions effective to enhance salt responsewas almost the same among Ca2+, Mg2+ and Na+ responses. Theresults suggest that a common mechanism is involved in the enhancementof Ca2+, Mg2+ and Na+ taste responses. The enhanced Mg2+ responseand the enhanced Na+ response were greatly inhibited by theaddition of Ca2+ ions, and the enhanced Ca2+ response was inhibitedby the addition of Mg2+ or Na+ ions, suggesting that competitiveantagonism occurs between Ca2+ and Mg2+ ions and between Ca2+and Na+ ions in the presence of Ni2+ ions. Ni2+ ions had a dualeffect on the Ca2+ response induced by low concentration (0.1mM) of CaCl2: enhancement at lower concentrations (0.020.1mM) of NiCl2 and inhibition at higher concentrations (0.55mM)of NiCl2. The present results suggest that transition metalions do not affect the receptor-antagonist complex, but affectonly the receptor-agonist complex. 相似文献
6.
Rat neurophysiological taste responses to salt solutions 总被引:1,自引:0,他引:1
1. Neurophysiological studies on the chemoresponsive tongueunits of the rat geniculate ganglion readily detected and furthercharacterized the two major functional neural groups designatedas acid and salt units by otherinvestigators in chorda tympani recordings. Units belongingto either of these groups were initially identified on the basisof their responses to a series of chemical solutions (a TestSeries) developed to distinguish unit groups in the geniculateganglion of the cat, dog and goat. 2. The nature of active ionicspecies effective in stimulating the units of the two differentgroups was further elaborated by studying their responses toa variety of salt solutions. From these studies, it was concludedthat the optimum molecular species for the acid units is anacid, where an acid is defined as a Br0nsted acid or protondonating molecule. A variety of molecular species may be activein solution, including some nitrogen compounds. Responses tosalt solutions by acid units are determined in part by the actionof the cation functioning as a Brønsted acid (NH4), orin promoting proton donor molecules in water (mainly H3O+).The salt units, on the other hand, are almost exclusively responsiveto solutions containing Na + and Li+. All other solutions werevirtually inactive. It was concluded that under a wide varietyof environmental conditions, Na+ would be the exclusive stimulusfor the salt units. Na+ and Li+ were found to be highly stimulatingwhen accompanied by a wide variety of solute anions, althoughthose containing the halogens (Cl, F, I,Br) were among the most stimulatory compounds tested.3. The establishment that the stimulus is a proton donor moleculefor the acid units and the Na+ and Li+ for the salt units hasprofound theoretical implications for the taste receptor. Biophysicalmodels of taste receptors are reviewed with respect to thisimproved understanding of the stimuli for the two types of units.It is suggested, after consideration of certain basic biochemicalaspects of the situation, that the acid receptor (possibly animidazole group) forms, as part of a protein, a proton conductingcircuit for driving an intracellular energy process devotedto proton sensing transmission. It is further suggested, inlight of the extreme specificity shown to Na +, that receptorattachment is of the multidentate ligand variety and is probablylinked to Na+, K+ transport across the cell membrane, as proposedby DeSimone et al. (1981). 相似文献
7.
Protease-activated receptor regulation of Cl- secretion in Calu-3 cells requires prostaglandin release and CFTR activation 总被引:1,自引:0,他引:1
Palmer ML Lee SY Maniak PJ Carlson D Fahrenkrug SC O'Grady SM 《American journal of physiology. Cell physiology》2006,290(4):C1189-C1198
Human lung epithelial (Calu-3) cells were used to investigate the effects of protease-activated receptor (PAR) stimulation on Cl secretion. Quantitative RT-PCR (QRT-PCR) showed that Calu-3 cells express PAR-1, -2, and -3 receptor mRNAs, with PAR-2 mRNA in greatest abundance. Addition of either thrombin or the PAR-2 agonist peptide SLIGRL to the basolateral solution of monolayers mounted in Ussing chambers produced a rapid increase in short-circuit current (Isc: thrombin, 21 ± 2 µA; SLIGRL, 83 ± 22 µA), which returned to baseline within 5 min after stimulation. Pretreatment of monolayers with the cell-permeant Ca2+-chelating agent BAPTA-AM (50 µM) abolished the increase in Isc produced by SLIGRL. When monolayers were treated with the cyclooxygenase inhibitor indomethacin (10 µM), nearly complete inhibition of both the thrombin- and SLIGRL-stimulated Isc was observed. In addition, basolateral treatment with the PGE2 receptor antagonist AH-6809 (25 µM) significantly inhibited the effects of SLIGRL on Isc. QRT-PCR revealed that Calu-3 cells express mRNAs for CFTR, the Ca2+-activated KCNN4 K+ channel, and the KCNQ1 K+ channel subunit, which, in association with KCNE3, is known to be regulated by cAMP. Stimulation with SLIGRL produced an increase in apical Cl conductance that was blocked in cells expressing short hairpin RNAs designed to target CFTR. These results support the conclusion that PAR stimulation of Cl secretion occurs by an indirect mechanism involving the synthesis and release of prostaglandins. In addition, PAR-stimulated Cl secretion requires activation of CFTR and at least two distinct K+ channels located in the basolateral membrane. cystic fibrosis transmembrane conductance regulator; KCNQ1; calcium-activated potassium channels; KCNN4; cAMP 相似文献
8.
Stimulus-induced currents in isolated taste receptor cells of the larval tiger salamander 总被引:3,自引:1,他引:2
Gustatory receptor cells, isolated from the lingual epitheliumof larval tiger salamanders (Ambystoma tigrinum), possess avariety of voltage- and ion-dependent conductances, includinga transient Na+ -current (INa), a voltage-gated Ca2+ -current(IA). a transient K+ -current (IA), a delayed rectifier K+ -current(IK), and a Ca2+ -activated K+ -current (IK(Ca))- By use ofwhole-cell and excised-patch tight-seal recording techniques,we examined the effects of taste stimuli on the conductancesof taste cells from the tiger salamander. Depolarizing receptorpotentials elicited by NaCl were associated with slow, gradedinward currents which were composed of amiloride-sensitive andtetrodoxin-(TTX)-sensitive components. Potassium chloride producedmaintained inward currents, which usually showed both phasicand tonic components and were only partially blocked by tetraethylammoniumchloride (TEA). Citric and acetic acids elicited slow depolarizationsin taste cells. Under voltage-clamp, acids produced graded inwardcurrents which were composed of two components: one attributableto a transient block of voltage-dependent K+ -channels and asmaller component which may have resulted from an increasedconductance to cations. Quinine hydrochloride elicited slowdepolarization of taste cells which was associated with a slowlydeveloping maintained inward current under voltage-clamp. Quininesuppressed both voltage-dependent inward and outward currents.In some taste cells, L-arginine elicited small outward currentswhich were attributable to an increase in K+ conductance. Inother cells, L-arginine produced a decrease in voltage-dependentoutward currents and generated depolarizations associated withinward currents. These results indicate that several independentmechanisms, including amiloride-sensitive Na+ -channels, andstimulus modulation of voltage-dependent K+ -channels, are involvedin taste cell responses to chemical stimuli. More than one mechanismis typically present in a single cell.
3Present address: Department of Physiology, Tokyo Medical andDental University, 5-45 Yushima 1-chome, Bunkyo-ku, Tokyo 113,Japan 相似文献
9.
Barrera NP Morales B Villalón M 《American journal of physiology. Cell physiology》2004,287(4):C1114-C1124
An increase in intracellular free Ca2+ concentration ([Ca2+]i) has been shown to be involved in the increase in ciliary beat frequency (CBF) in response to ATP; however, the signaling pathways associated with inositol 1,4,5-trisphosphate (IP3) receptor-dependent Ca2+ mobilization remain unresolved. Using radioimmunoassay techniques, we have demonstrated the appearance of two IP3 peaks occurring 10 and 60 s after ATP addition, which was strongly correlated with a release of intracellular Ca2+ from internal stores and an influx of extracellular Ca2+, respectively. In addition, ATP-dependent Ca2+ mobilization required protein kinase C (PKC) and Ca2+/calmodulin-dependent protein kinase II activation. We found an increase in PKC activity in response to ATP, with a peak at 60 s after ATP addition. Xestospongin C, an IP3 receptor blocker, significantly diminished both the ATP-induced increase in CBF and the initial transient [Ca2+]i component. ATP addition in the presence of xestospongin C or thapsigargin revealed that the Ca2+ influx is also dependent on IP3 receptor activation. Immunofluorescence and confocal microscopic studies showed the presence of IP3 receptor types 1 and 3 in cultured ciliated cells. Immunogold electron microscopy localized IP3 receptor type 3 to the nucleus, the endoplasmic reticulum, and, interestingly, the plasma membrane. In contrast, IP3 receptor type 1 was found exclusively in the nucleus and the endoplasmic reticulum. Our study demonstrates for the first time the presence of IP3 receptor type 3 in the plasma membrane in ciliated cells and leads us to postulate that the IP3 receptor can directly trigger Ca2+ influx in response to ATP. transduction mechanisms; P2Y receptor; calcium influx 相似文献
10.
Putnam RW Filosa JA Ritucci NA 《American journal of physiology. Cell physiology》2004,287(6):C1493-C1526
An increase in CO2/H+ is a major stimulus for increased ventilation and is sensed by specialized brain stem neurons called central chemosensitive neurons. These neurons appear to be spread among numerous brain stem regions, and neurons from different regions have different levels of chemosensitivity. Early studies implicated changes of pH as playing a role in chemosensitive signaling, most likely by inhibiting a K+ channel, depolarizing chemosensitive neurons, and thereby increasing their firing rate. Considerable progress has been made over the past decade in understanding the cellular mechanisms of chemosensitive signaling using reduced preparations. Recent evidence has pointed to an important role of changes of intracellular pH in the response of central chemosensitive neurons to increased CO2/H+ levels. The signaling mechanisms for chemosensitivity may also involve changes of extracellular pH, intracellular Ca2+, gap junctions, oxidative stress, glial cells, bicarbonate, CO2, and neurotransmitters. The normal target for these signals is generally believed to be a K+ channel, although it is likely that many K+ channels as well as Ca2+ channels are involved as targets of chemosensitive signals. The results of studies of cellular signaling in central chemosensitive neurons are compared with results in other CO2- and/or H+-sensitive cells, including peripheral chemoreceptors (carotid body glomus cells), invertebrate central chemoreceptors, avian intrapulmonary chemoreceptors, acid-sensitive taste receptor cells on the tongue, and pain-sensitive nociceptors. A multiple factors model is proposed for central chemosensitive neurons in which multiple signals that affect multiple ion channel targets result in the final neuronal response to changes in CO2/H+. hypercapnia; brain stem; ventilation; peripheral chemoreceptor; glia; gap junction; glomus; channel; calcium; potassium; carbonic anhydrase; taste receptor; nociception 相似文献
11.
Trubey KR Culpepper S Maruyama Y Kinnamon SC Chaudhari N 《American journal of physiology. Cell physiology》2006,291(2):C237-C244
We previously showed that rat taste buds express several adenylyl cyclases (ACs) of which only AC8 is known to be stimulated by Ca2+. Here we demonstrate by direct measurements of cAMP levels that AC activity in taste buds is stimulated by treatments that elevate intracellular Ca2+. Specifically, 5 µM thapsigargin or 3 µM A-23187 (calcium ionophore), both of which increase intracellular Ca2+ concentration ([Ca2+]i), lead to a significant elevation of cAMP levels. This calcium stimulation of AC activity requires extracellular Ca2+, suggesting that it is dependent on Ca2+ entry rather than release from stores. With immunofluorescence microscopy, we show that the calcium-stimulated AC8 is principally expressed in taste cells that also express phospholipase C2 (i.e., cells that elevate [Ca2+]i in response to sweet, bitter, or umami stimuli). Taste transduction for sucrose is known to result in an elevation of both cAMP and calcium in taste buds. Thus we tested whether the cAMP increase in response to sucrose is a downstream consequence of calcium elevation. Even under conditions of depletion of stored and extracellular calcium, the cAMP response to sucrose stimulation persists in taste cells. The cAMP signal in response to monosodium glutamate stimulation is similarly unperturbed by calcium depletion. Our results suggest that tastant-evoked cAMP signals are not simply a secondary consequence of calcium modulation. Instead, cAMP and released Ca2+ may represent independent second messenger signals downstream of taste receptors. calcium-sensitive adenylyl cyclase; capacitative entry; cross talk; taste transduction 相似文献
12.
The role of Cl in the reactivation of O2 evolution inphotosystem II (PS II) particles derived from spinach chloroplastswas studied in the presence of various salts. Multivalent ion(especially anion) salts were found to strongly suppress thereactivation of O2 evolution by Cl in the Cl-depletedPS II particles in a competitive manner. The effectiveness ofanions in the suppression of Cl-supported O2 evolutionwas in the order of trivalent>divalent>monovalent ones.Multivalent anions similarly suppressed O2 evolution in theuntreated PS II particles under low and moderate Cl concentrations.pH dependence of the Cl-affinity (Km) value for Cl)was also studied. Within the pH range 5.5 to 8 the Km valuebecame higher as the pH of the medium increased. These resultssuggest that the membrane surface in the vicinity of the Claction site is net positively charged and attracts Clelectrostatically, and that the site is almost freely accessibleto various anions. The origin and role of the local net positivedomain and the role of peripheral proteins are discussed. (Received May 27, 1985; Accepted October 8, 1985) 相似文献
13.
To examine the relationship between H+-ATPase and the transportof anions, we investigated the effects of various inhibitorson the activity of the H+-ATPase, the transport of protons,and the transport of Cl- ions using plasma membrane vesiclesprepared from barley roots. Some inhibitors, namely, 4,4-diisothiocyano-2,2-stilbenedisulfonate (DIDS) and Zn2+ ions markedly inhibited H+- ATPaseactivity. Other compounds, such as phenylglyoxal (PGO) and niflumicacid (NIF), inhibited H+-ATPase activity by 20-30%, while anthracene-9-carboxylate(A-9-C) and tetraethylammonium chloride (TEA-Cl) had littleeffect on this activity. The ATP-dependent acidification ofthe interior of vesicles was strongly dependent on the presenceof permeant anions, such as chloride (Cl-) and nitrate (NO3-),and it was completely inhibited by 0.2 mM NIF. Other compounds,namely, A-9-C of 0.1 mM and TEA-Cl of 10 mM, did not affectH+-transport activity. The inhibition of H+-transport activityby NIF was observed even when the activity was assayed in thepresence of KCl, KNO3, or bis-tris-propane (BTP)-Cl. Using 36cl,we quantified Cl--transport activity by measuring the uptakeof Cl- ions into the plasma membrane vesicles. The uptake dependedon the potential difference across the membrane that was generatedby H+-ATPase; it was enhanced by an inside-positive potentialgradient. At 0.1 mM, NIF completely blocked the voltage-dependentCl--transport activity. From these properties of the Cl- transporterand the inhibition of H+-transport activity by NIF, we suggestthat H+-transport activity across the plasma membrane mightbe modulated by the transport of anions via a NIF-sensitiveanion-permeable transporter that acts to collapse the inside-positivepotential generated by H+-ATPase. (Received September 7, 1995; Accepted July 23, 1996) 相似文献
14.
Distinct pharmacological properties of ET-1 and ET-3 on astroglial gap junctions and Ca2+ signaling 总被引:3,自引:0,他引:3
Blomstrand Fredrik; Giaume Christian; Hansson Elisabeth; Ronnback Lars 《American journal of physiology. Cell physiology》1999,277(4):C616
Astrocytes represent a major target for endothelins (ETs), afamily of peptides that have potent and multiple effects on signal transduction pathways and can be released by several cell types in thebrain. In the present study we have investigated the involvement ofdifferent ET receptor subtypes on intercellular dye diffusion, intracellular Ca2+homeostasis, and intercellularCa2+ signaling in cultured ratastrocytes from hippocampus and striatum. Depending on the ETconcentration and the receptor involved, ET-1- and ET-3-inducedintracellular Ca2+ increases withdifferent response patterns. Both ET-1 and ET-3 are powerful inhibitorsof gap junctional permeability and intercellular Ca2+ signaling. The nonselectiveET receptor agonist sarafotoxin S6b and theETB receptor-selective agonist IRL1620 mimicked these inhibitions. The ET-3 effects were only marginallyaffected by an ETA receptorantagonist but completely blocked by anETB receptor antagonist. However,the ET-1-induced inhibition of gap junctional dye transfer andintercellular Ca2+ signaling wasonly marginally blocked by ETA orETB receptor-selective antagonistsbut fully prevented when these antagonists were applied together. TheET-induced inhibition of gap junction permeability and intercellularCa2+ signaling indicates thatimportant changes in the function of astroglial communication mightoccur when the level of ETs in the brain is increased. 相似文献
15.
The major rate limiting steps in bullfrog peripheral nerve gustatoryresponse latencies were studied by measuring glossopharyngealnerve multi-unit activity, detecting response onset times, andcalculating rates of stimulus diffusion to receptor cells andsignal propagation along first order neurons. The stimulus deliverytechnique minimized physicochemical and mechanical artifacts,as well as neural responses to mechanical stimulation of thetongue. Neural activity was processed in 10 ms bins. Responseonsets were determined by a criterion that compared the statisticalprobability of the neural events during stimulus liquid presentationswith those during both Ringer's solution presentations afteradaptation to Ringer's and no-stimulus control conditions. Thiscriterion yielded response latencies of 70110 ms for10 mM CaCl2, 2 mM quinine hydrochloride, and 105 M and106 M cantharidin or Ringer's, and H2O. No responsesoccurred during presentations of 107 M cantharidin orRinger's after adaptation to Ringer's, or during the no-stimuluscontrol condition. From the measured latencies and calculatedrates of stimulus diffusion to receptor cells, and signal propagationalong first order neurons, we conclude that taste receptor cellevents and not perireceptor or signal propagatiog events arethe major rate limiting steps in gustatory response latencies. 相似文献
16.
RNA interference targeted to multiple P2X receptor subtypes attenuates zinc-induced calcium entry 总被引:2,自引:0,他引:2
Liang L Zsembery A Schwiebert EM 《American journal of physiology. Cell physiology》2005,289(2):C388-C396
A postulated therapeutic avenue in cystic fibrosis (CF) is activation of Ca2+-dependent Cl channels via stimulation of Ca2+ entry from extracellular solutions independent of CFTR functional status. We have shown that extracellular zinc and ATP induce a sustained increase in cytosolic Ca2+ in human airway epithelial cells that translates into stimulation of sustained secretory Cl transport in non-CF and CF human and mouse airway epithelial cells, cell monolayers, and nasal mucosa. On the basis of these studies, the Ca2+ entry channels most likely involved were P2X purinergic receptor channels. In the present study, molecular and biochemical data show coexpression of P2X4, P2X5, and P2X6 subtypes in non-CF (16HBE14o) and CF (IB3-1) human bronchial epithelial cells. Other P2X receptor Ca2+ entry channel subtypes are expressed rarely or not at all in airway epithelia, epithelial cell models from other CF-relevant tissues, or vascular endothelia. Novel transient lipid transfection-mediated delivery of small interference RNA fragments specific to P2X4 and P2X6 (but not P2X5) into IB3-1 CF human airway epithelial cells inhibited extracellular zinc- and ATP-induced Ca2+ entry markedly in fura-2 Ca2+ measurements and "knocked down" protein by >65%. These data suggest that multiple P2X receptor Ca2+ entry channel subtypes are expressed in airway epithelia. P2X4 and P2X6 may coassemble on the airway surface as targets for possible therapeutics for CF independent of CFTR genotype. purinergic receptors; zinc receptors; airway epithelia; cystic fibrosis; therapy 相似文献
17.
The dependence of membrane potentials on changes in the extra-cellularK+ concentration [K+]e was investigated in potato tuber sliceswith dripping perfusion, and in growing Vigna hypocotyl segmentswith pressurized intra-organ perfusion methods. Only under anoxiawere the membrane potential of potato tuber slices and the electricpotential difference between the parenchyma symplast and xylem(Vpx) of Vigna hypocotyl segments depolarized markedly (46 mVand 42 mV/log[K+]e unit, respectively) with increasing [K+]eabove the critical values. The electric potential differencebetween the parenchyma symplast and organ surface (Vps of thehypocotyl segments remained nearly unchanged up to 30 mEq [K+]e.Under highly aerobic conditions the membrane potentials wererelatively independent of [K+]e except at very high K+ concentrations.Vps showed even hyperpolarization with the increasing KCl concentrationin the perfusion solution that is not in direct contact withthe surface membrane of the parenchyma symplast. The respiration-dependentelectrogenic components of the membrane potentials regularlyincreased with the increasing [K+]e. A voltage-dependent homeostaticcontrol of membrane potential is discussed. (Received August 13, 1984; Accepted December 21, 1984) 相似文献
18.
Membrane Depolarization and the Metabolism of Muscle 总被引:1,自引:0,他引:1
The respiration of frog twitch muscles rises markedly when [K]0israised; respiration is stimulated by levels of [K]0 below thethreshold for contracture(Fenn, 1931).Respiration is also stimulatedby elevated [Rb]0 and [Cs]0 in direct relation to their abilityto depolarize the membrane. Respiration is stimulated even whenthe anions in the high [K]o solution cannot permeate the membrane.If[K]0is raised to 25 mM there is an increase in respiration whichis sustained for hours. If [K]0is 30 mM or above, there is atransitory burst of stimulated respiration followed by a declineback to the basal level. The response to elevated[K]0 can beblocked by divalent cations or by local anesthetics; the blockingagents act rapidly, probably on the cell membrane. Either extracellularcalcium or strontium is needed for a prolonged stimulation ofrespiration. Depolarization seems to increase respiration bycausing the release of calcium into the sarcoplasm. Since respirationis increased by a depolarization below the threshold for producinga contracture, respiration is a sensitive indicator of the sarcoplasmicconcentration of calcium. A model for the relation between sarcoplasmic[Ca] and membrane potential is proposed. Calcium can be releasedfrom a store in the cell, the released Ca++ entering the sarcoplasm.The store is replenished by Ca++ entering the fiber from theextracellular solution. When the membrane is depolarized, therate of release of calcium in the store is increased; at thesame time the rate at which extracellular calcium can replenishthe store is decreased.This model accounts well for the dataon respiration and also for the contractures of single musclefibers. Calcium probably acts within the cell to activate anATP-ase which causes an increase in ADP and hence an increasein respiration. Other investigators have found changes in theactivity of certain enzymes and in the permeability of the membrane;possibly these changes are also a direct response to an increasein sarcoplasmic calcium. 相似文献
19.
A P2X7 receptor stimulates plasma membrane trafficking in the FRTL rat thyrocyte cell line 总被引:1,自引:0,他引:1
Thyroid cells express a variety of P2Y and P2X purinergic receptor subtypes. G protein-coupled P2Y receptors influence a wide variety of thyrocyte-specific functions; however, functional P2X receptor-gated channels have not been observed. In this study, we used whole cell patch-clamp recording and fluorescence imaging of the plasma membrane marker FM1-43 to examine the effects of extracellular ATP on membrane permeability and trafficking in the Fisher rat thyroid cell line FRTL. We found a cation-selective current that was gated by ATP and 2',3'-O-(4-benzoylbenzoyl)-ATP but not by UTP. The ATP-evoked currents were inhibited by pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid, adenosine 5'-triphosphate-2',3'-dialdehyde, 100 µM Zn2+, and 50 µM Cu2+. Fluorescence imaging revealed pronounced, temperature-sensitive stimulation of exocytosis and membrane internalization by ATP with the same pharmacological profile as observed for activation of current. The EC50 for ATP stimulation of internalization was 440 µM in saline containing 2 mM Ca2+ and 2 mM Mg2+, and 33 µM in low-Mg2+, nominally Ca2+-free saline. Overall, the results are most consistent with activation of a P2X7 receptor by ATP4. However, low permeability to N-methyl-D-glucamine+ and the propidium cation YO-PRO-1 indicates absence of the cytolytic pore that often accompanies P2X7 receptor activation. ATP stimulation of internalization occurs in Na+-free, Ca2+-free, or low-Mg2+ saline and therefore does not depend on cation influx through the ATP-gated channel. We conclude that ATP activation of a P2X7 receptor stimulates membrane internalization in FRTL cells via a transduction pathway that does not depend on cation influx. purinergic receptor; internalization; patch clamp 相似文献
20.
We examined the effects of dissolved nitric oxide (NO) gas oncytoplasmic calcium levels ([Ca2+]i) in C6glioma cells under anoxic conditions. The maximum elevation (27 ± 3 nM) of [Ca2+]i was reached at 10 µM NO. Asecond application of NO was ineffective if the first was >0.5 µM.The NO donor diethylamine/NO mimicked the effects of NO. Acute exposureof the cells to low calcium levels was without effect on the NO-evokedresponse. Thapsigargin (TG) increased [Ca2+]iand was less effective if cells were pretreated with NO. Hemoglobin inhibited the effects of NO at a molar ratio of 10:1. 8-Bromo-cGMP waswithout effect on the NO-evoked response. If cells were pretreated withTG or exposed chronically to nominal amounts of calcium, NO decreased[Ca2+]i. The results suggest that C6 gliomacells have two receptors for NO. One receptor (NOA)elevates [Ca2+]i and resides on theendoplasmic reticulum (ER). The other receptor (NOB)decreases [Ca2+]i and resides on theplasmalemma or the ER. The latter receptor dominates when the level ofcalcium within intracellular stores is diminished. 相似文献