共查询到20条相似文献,搜索用时 15 毫秒
1.
I R Mellor M S Sansom 《Proceedings of the Royal Society of London. Series B, Containing papers of a Biological character. Royal Society (Great Britain)》1990,239(1296):383-400
Mastoparan, a 14-residue peptide, has been investigated with respect to its ability to form ion channels in planar lipid bilayers. In the presence of 0.3-3.0 microM mastoparan, two types of activity are seen. Type I activity is characterized by discrete channel openings, exhibiting multiple conductance levels in the range 15-700 pS. Type II activity is characterized by transient increases in bilayer conductance, up to a maximum of about 650 pS. Both type I and type II activities are voltage dependent. Channel activation occurs if the compartment containing mastoparan is held at a positive potential; channel inactivation if the same compartment is held at a negative potential. Channel formation is dependent on ionic strength; channel openings are only observed at KCl concentrations of 0.3 M or above. Furthermore, raising the concentration of KCl to 3.0 M stabilizes the open form of the channel. Mastoparan channels are weakly cation selective, PK/Cl approximately 2. A 12-residue analogue, des-Ile1,Asn2-mastoparan, preferentially forms type I channels. The ion channels formed by these short peptides may be modelled in terms of bundles of transmembrane alpha-helices. 相似文献
2.
《The Journal of general physiology》1995,105(2):227-247
The purpose of this study was to use whole-cell and cell-attached patches of cultured skeletal muscle myotubes to study the macroscopic and unitary behavior of voltage-dependent calcium channels under similar conditions. With 110 mM BaCl2 as the charge carrier, two types of calcium channels with markedly different single-channel and macroscopic properties were found. One class was DHP-insensitive, had a single-channel conductance of approximately 9 pS, yielded ensembles that displayed an activation threshold near -40 mV, and activated and inactivated rapidly in a voltage-dependent manner (T current). The second class could only be well resolved in the presence of the DHP agonist Bay K 8644 (5 microM) and had a single-channel conductance of approximately 14 pS (L current). The 14-pS channel produced ensembles exhibiting a threshold of approximately -10 mV that activated slowly (tau act approximately 20 ms) and displayed little inactivation. Moreover, the DHP antagonist, (+)-PN 200-110 (10 microM), greatly increased the percentage of null sweeps seen with the 14-pS channel. The open probability versus voltage relationship of the 14-pS channel was fitted by a Boltzmann distribution with a VP0.5 = 6.2 mV and kp = 5.3 mV. L current recorded from whole-cell experiments in the presence of 110 mM BaCl2 + 5 microM Bay K 8644 displayed similar time- and voltage-dependent properties as ensembles of the 14-pS channel. Thus, these data are the first comparison under similar conditions of the single-channel and macroscopic properties of T current and L current in native skeletal muscle, and identify the 9- and 14-pS channels as the single-channel correlates of T current and L current, respectively. 相似文献
3.
《The Journal of general physiology》1991,98(5):921-939
Two K(+)-selective channels in neonatal rat atrial cells activated by lipophilic compounds have been characterized in detail. The arachidonic acid-stimulated channel (IK.AA) had a slope conductance of 124 +/- 17 pS at +30 mV in symmetrical 140 mM potassium and a mean open time of approximately 1 ms, and was relatively voltage independent. IK.AA activity was reversibly increased by lowering pH to 6.0. Arachidonic acid was most effective in activating this channel, although a number of lipophilic compounds resulted in activation. Surprisingly, choline, a polar molecule, also activated the channel. A second K+ channel was activated by 10 microM phosphatidylcholine applied to the intracellular surface of inside-out atrial patches. This channel (IK.PC) had a slope conductance of 60 +/- 6 pS at +40 mV and a mean open time of approximately 0.6 ms, and was also relatively voltage independent. Fatty acids are probably monomeric in the membrane under the conditions of our recording; thus detergent effects are unlikely. Since a number of compounds including fatty acids and prostaglandins activated these two channels, an indirect, channel-specific mechanism may account for activation of these two cardiac K+ channels. 相似文献
4.
The effect of amphiphilic cationic drugs on the channel activity of the mitochondrial inner membrane was examined with patch-clamp techniques. The therapeutic drugs amiodarone, propranolol and quinine reduced the probability of being open for the multiconductance channel (MCC) activity (levels from 30 pS to over 1 nS). While amiodarone decreased the probability of being open for the voltage dependent approximately 100 pS channel, it increased the conductance 42 +/- 20% (mean +/- SD, n = 6) with no significant change in mean open time. Similar results were obtained with propranolol. These data indicate that the approximately 100 pS channel is distinct from MCC activity. 相似文献
5.
The single channel properties of recombinant gamma-aminobutyric acid type A (GABA(A))alphabetagamma receptors co-expressed with the trafficking protein GABARAP were investigated using membrane patches in the outside-out patch clamp configuration from transiently transfected L929 cells. In control cells expressing alphabetagamma receptors alone, GABA activated single channels whose main conductance was 30 picosiemens (pS) with a subconductance state of 20 pS, and increasing the GABA concentration did not alter their conductance. In contrast, when GABA(A) receptors were co-expressed with GABARAP, the GABA-activated single channels displayed multiple, high conductances (> or =40 pS), and GABA (> or =10 microM) was able to increase their conductance, up to a maximum of 60 pS. The mean open time of GABA-activated channels in control cells expressing alphabetagamma receptors alone was 2.3 +/- 0.1 ms for the main 30-pS channel and shorter for the subconductance state (20 pS, 0.8 +/- 0.1 ms). Similar values were measured for the 30- and 20-pS channels active in patches from cells co-expressing GABARAP. However higher conductance channels (> or =40 pS) remained open longer, irrespective of whether GABA or GABA plus diazepam activated them. Plotting mean open times against mean conductances revealed a linear relationship between these two parameters. Since high GABA concentrations increase both the maximum single channel conductance and mean open time of GABA(A) channels co-expressed with GABARAP, trafficking processes must influence ion channel properties. This suggests that the organization of extrasynaptic GABA(A) receptors may provide a range of distinct inhibitory currents in the brain and, further, provide differential drug responses. 相似文献
6.
The subcellular location and some properties of the rat kidney 25-hydroxyvitamin D3-1 alpha-hydroxylase are described. Enzyme activity can be measured as previously discussed (Tanaka, Y., and DeLuca, H.F. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 196-199) using saturating substrate (25-hydroxyvitamin D3) concentrations. The reaction is linear with time for up to 30 min at a substrate concentration of 80 microM and 9-11 mg/ml mitochondrial protein. The enzyme, located in the mitochondria, requires molecular oxygen and a source of NADPH. Succinate supplies NADPH for 1 alpha-hydroxylation through reversal of electron transport and transhydrogenation as shown by inhibition with antimycin A and dinitrophenol. Malate supplies NADPH for the reaction via the mitochondrial malic enzyme or malate dehydrogenase and transhydrogenase as indicated by the lack of inhibition by antimycin A but inhibition with dinitrophenol. Metyrapone and carbon monoxide both inhibit 1 alpha-hydroxylation indicating the involvement of cytochrome P-450. Diphenyl-p-phenylenediamine, a lipid peroxidase inhibitor, has no effect on 1 alpha-hydroxylation. 相似文献
7.
Bao HF Liu L Self J Duke BJ Ueno R Eaton DC 《American journal of physiology. Gastrointestinal and liver physiology》2008,295(2):G234-G251
The bicyclic fatty acid lubiprostone (formerly known as SPI-0211) activates two types of anion channels in A6 cells. Both channel types are rarely, if ever, observed in untreated cells. The first channel type was activated at low concentrations of lubiprostone (<100 nM) in >80% of cell-attached patches and had a unit conductance of approximately 3-4 pS. The second channel type required higher concentrations (>100 nM) of lubiprostone to activate, was observed in approximately 30% of patches, and had a unit conductance of 8-9 pS. The properties of the first type of channel were consistent with ClC-2 and the second with CFTR. ClC-2's unit current strongly inwardly rectified that could be best fit by models of the channel with multiple energy barrier and multiple anion binding sites in the conductance pore. The open probability and mean open time of ClC-2 was voltage dependent, decreasing dramatically as the patches were depolarized. The order of anion selectivity for ClC-2 was Cl > Br > NO(3) > I > SCN, where SCN is thiocyanate. ClC-2 was a "double-barreled" channel favoring even numbers of levels over odd numbers as if the channel protein had two conductance pathways that opened independently of one another. The channel could be, at least, partially blocked by glibenclamide. The properties of the channel in A6 cells were indistinguishable from ClC-2 channels stably transfected in HEK293 cells. CFTR in the patches had a selectivity of Cl > Br > NO(3) congruent with SCN congruent with I. It outwardly rectified as expected for a single-site anion channel. Because of its properties, ClC-2 is uniquely suitable to promote anion secretion with little anion reabsorption. CFTR, on the other hand, could promote either reabsorption or secretion depending on the anion driving forces. 相似文献
8.
Effects of local anesthetics on single channel behavior of skeletal muscle calcium release channel 总被引:13,自引:1,他引:12
《The Journal of general physiology》1993,101(2):207-233
The effects of the two local anesthetics tetracaine and procaine and a quaternary amine derivative of lidocaine, QX314, on sarcoplasmic reticulum (SR) Ca2+ release have been examined by incorporating the purified rabbit skeletal muscle Ca2+ release channel complex into planar lipid bilayers. Recordings of potassium ion currents through single channels showed that Ca(2+)- and ATP-gated channel activity was reduced by the addition of the tertiary amines tetracaine and procaine to the cis (cytoplasmic side of SR membrane) or trans (SR lumenal) side of the bilayer. Channel open probability was lowered twofold at tetracaine and procaine concentrations of approximately 150 microM and 4 mM, respectively. Hill coefficients of 2.0 and greater indicated that the two drugs inhibited channel activity by binding to two or more cooperatively interacting sites. Unitary conductance of the K(+)- conducting channel was not changed by 1 mM tetracaine in the cis and trans chambers. In contrast, cis millimolar concentrations of the quaternary amine QX314 induced a fast blocking effect at positive holding potentials without an apparent change in channel open probability. A voltage-dependent block was observed at high concentrations (millimolar) of tetracaine, procaine, and QX314 in the presence of 2 microM ryanodine which induced the formation of a long open subconductance. Vesicle-45Ca2+ ion flux measurements also indicated an inhibition of the SR Ca2+ release channel by tetracaine and procaine. These results indicate that local anesthetics bind to two or more cooperatively interacting high-affinity regulatory sites of the Ca2+ release channel in or close to the SR membrane. Voltage-dependent blockade of the channel by QX314 in the absence of ryanodine, and by QX314, procaine and tetracaine in the presence of ryanodine, indicated one low-affinity site within the conduction pathway of the channel. Our results further suggest that tetracaine and procaine may primarily inhibit excitation-contraction coupling in skeletal muscle by binding to the high-affinity, regulatory sites of the SR Ca2+ release channel. 相似文献
9.
Siemen D Loupatatzis C Borecky J Gulbins E Lang F 《Biochemical and biophysical research communications》1999,257(2):549-554
A single channel current was recorded from mitoplasts (i.e., inner mitochondrial membrane) of the human glioma cell line LN229 using patch-clamp techniques in the mitoplast-attached mode. We frequently found a 295 +/- 18 pS channel that showed a straight i-E relation in the range +/-60 mV in 150 mM KCl solutions on either side of the mitoplast. If KCl in the bath was exchanged against NaCl, outward currents were undetectable, indicating potassium selectivity. Channel activity determined as open probability increased with increasing Ca2+ concentrations (EC50 = 0.9 microM at 60 mV). Open probability was voltage dependent. An e-fold increase of time spent in the open state was induced by a depolarization of 10.5 mV. Open probability was decreased by charybdotoxin concentration and voltage dependently (EC50 = 1.4 nM). In conclusion, we show for the first time that the inner mitochondrial membrane in human glioma cells contains a calcium-dependent K channel of the BK-type. 相似文献
10.
Blair KL Geary TG Mensch SK Vidmar TJ Li SK Ho NF Thompson DP 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2003,134(4):805-818
Patch-clamp recordings from muscle- and cuticle-facing hypodermal membranes of the gastrointestinal nematode Ascaris suum reveal a high-conductance, voltage- sensitive Ca(2+) -dependent Cl(-) channel. The hypodermal channel has a conductance of 195 pS in symmetrical 160 mM NaCl. The open probability of the channel is highly voltage-sensitive, and channel activity is not observed when Ca(2+) is reduced to <100 microM. The channel is permeable to organic anions that are major end-products of carbohydrate metabolism in A. suum, including acetate, butyrate and 2-methylvalerate. The conductances and relative permeabilities of these organic anions are inversely related to size, with 2-methylvalerate being only approximately 3% as permeable as Cl(-). The diameter of the channel pore was 12.3+/-0.2 A, calculated from the relative permeability coefficients of Cl(-) and the organic anions. Results of this study are consistent with the hypothesis that the large conductance anion channel in A. suum hypodermal membranes provides a low energy pathway for organic anion excretion from the hypodermal compartment, followed by diffusion across the aqueous channels of the cuticle matrix. 相似文献
11.
Binding of an odorant to its receptor activates the cAMP-dependent pathway, and also leads to inositol 1,4,5-trisphosphate (InsP(3)) production. This induces opening of a plasma membrane channel in olfactory receptor cells (ORCs). We investigated single-channel properties of this channel in the presence of a phospholipase C (PLC) activator (imipramine) and of a potent activator of the InsP(3)/Ca(2+) release channel (adenophostin A) by reconstituting carp olfactory cilia into planar lipid bilayers. In the presence of 53 mM barium as a charge carrier, the addition of 50 microM imipramine induced a current of 1.53+/-0.05 pA at 0 mV. There were two different mean open times (6.0+/-0.6 ms and 49.6+/-6.4 ms). The I/ V curve displayed a slope conductance of 50+/-2 pS. Channel activity was transient and was blocked by neomycin (50 microM). These observations suggest that imipramine may activate the olfactory InsP(3)-gated channel through PLC. Using the same ionic conditions, the application of 0.5 microM adenophostin A triggered a current of 1.47+/-0.04 pA at 0 mV. The I/ V curve displayed a slope conductance of 60+/-2 pS. This channel showed only a single mean open time (15.0+/-0.3 ms) and was strongly inhibited by ruthenium red (30 microM) and heparin (10 microg/mL). These results indicate that adenophostin A and imipramine may act on the ciliary InsP(3)-gated channel and are potentially valuable pharmacological tools for studying olfactory transduction mechanisms. 相似文献
12.
1. In mitochondrial particles antimycin binds to two separate specific sites with dissociation constants KD1 less than 4 - 10(-13) M and KD2 = 3 - 10(-9) M, respectively. 2. The concentrations of the two antimycin binding sites are about equal. The absolute concentration for each binding site is about 100 - 150 pmol per mg of mitochondrial protein. 3. Antimycin bound to the stronger site mainly inhibits NADH-and succinate oxidase. Binding of antimycin to the weaker binding site inhibits the electron flux to exogenously added cytochrome c after blocking cytochrome oxidase by KCN. 4. Under certain conditions cytochrome b and c1 are dispensible components for antimycin-sensitive electron transport. 5. A model of the respiratory chain in yeast is proposed which accounts for the results reported here and previously. (Lang, B., Burger, G., and Bandlow, W. (1974) Biochim. Biophys. Acta 368, 71-85). 相似文献
13.
Acetylcholine receptor in planar lipid bilayers. Characterization of the channel properties of the purified nicotinic acetylcholine receptor from Torpedo californica reconstituted in planar lipid bilayers 总被引:4,自引:1,他引:3
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The properties of the channel of the purified acetylcholine receptor (AChR) were investigated after reconstitution in planar lipid bilayers. The time course of the agonist-induced conductance exhibits a transient peak that relaxes to a steady state value. The macroscopic steady state membrane conductance increases with agonist concentration, reaching saturation at 10(-5) M for carbamylcholine (CCh). The agonist-induced membrane conductance was inhibited by d-tubocurarine (50% inhibition, IC50, at approximately 10(-6) M) and hexamethonium (IC50 approximately 10(-5) M). The single channel conductance, gamma, is ohmic and independent of the agonist. At 0.3 M monovalent salt concentrations, gamma = 28 pS for Na+, 30 pS for Rb+, 38 pS for Cs+, and 50 pS for NH+4. The distribution of channel open times was fit by a sum of two exponentials, reflecting the existence of two distinct open states. tau o1 and tau o2, the fast and slow components of the distribution of open times, are independent of the agonist concentration: for CCh this was verified in the range of 10(-6) M less than C less than 10(-3)M. tau 01 and tau o2 are approximately three times longer for suberyldicholine ( SubCh ) than for CCh. tau o1 and tau o2 are moderately voltage dependent, increasing as the applied voltage in the compartment containing agonist is made more positive with respect to the other. At desensitizing concentrations of agonist, the AChR channel openings occurred in a characteristic pattern of sudden paroxysms of channel activity followed by quiescent periods. A local anesthetic derivative of lidocaine ( QX -222) reduced both tau o1 and tau o2. This effect was dependent on both the concentration of QX -222 and the applied voltage. Thus, the AChR purified from Torpedo electric organ and reconstituted in planar lipid bilayers exhibits ion conduction and kinetic and pharmacological properties similar to AChR in intact muscle postsynaptic membranes. 相似文献
14.
Agonist-dependent single channel current and gating in alpha4beta2delta and alpha1beta2gamma2S GABAA receptors
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The family of gamma-aminobutyric acid type A receptors (GABA(A)Rs) mediates two types of inhibition in the mammalian brain. Phasic inhibition is mediated by synaptic GABA(A)Rs that are mainly comprised of alpha(1), beta(2), and gamma(2) subunits, whereas tonic inhibition is mediated by extrasynaptic GABA(A)Rs comprised of alpha(4/6), beta(2), and delta subunits. We investigated the activation properties of recombinant alpha(4)beta(2)delta and alpha(1)beta(2)gamma(2S) GABA(A)Rs in response to GABA and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3(2H)-one (THIP) using electrophysiological recordings from outside-out membrane patches. Rapid agonist application experiments indicated that THIP produced faster opening rates at alpha(4)beta(2)delta GABA(A)Rs (beta approximately 1600 s(-1)) than at alpha(1)beta(2)gamma(2S) GABA(A)Rs (beta approximately 460 s(-1)), whereas GABA activated alpha(1)beta(2)gamma(2S) GABA(A)Rs more rapidly (beta approximately 1800 s(-1)) than alpha(4)beta(2)delta GABA(A)Rs (beta < 440 s(-1)). Single channel recordings of alpha(1)beta(2)gamma(2S) and alpha(4)beta(2)delta GABA(A)Rs showed that both channels open to a main conductance state of approximately 25 pS at -70 mV when activated by GABA and low concentrations of THIP, whereas saturating concentrations of THIP elicited approximately 36 pS openings at both channels. Saturating concentrations of GABA elicited brief (<10 ms) openings with low intraburst open probability (P(O) approximately 0.3) at alpha(4)beta(2)delta GABA(A)Rs and at least two "modes" of single channel bursting activity, lasting approximately 100 ms at alpha(1)beta(2)gamma(2S) GABA(A)Rs. The most prevalent bursting mode had a P(O) of approximately 0.7 and was described by a reaction scheme with three open and three shut states, whereas the "high" P(O) mode ( approximately 0.9) was characterized by two shut and three open states. Single channel activity elicited by THIP in alpha(4)beta(2)delta and alpha(1)beta(2)gamma(2S) GABA(A)Rs occurred as a single population of bursts (P(O) approximately 0.4-0.5) of moderate duration (approximately 33 ms) that could be described by schemes containing two shut and two open states for both GABA(A)Rs. Our data identify kinetic properties that are receptor-subtype specific and others that are agonist specific, including unitary conductance. 相似文献
15.
Functionally distinct phospho-forms underlie incremental activation of protein kinase-regulated Cl- conductance in mammalian heart 总被引:11,自引:3,他引:8
《The Journal of general physiology》1993,101(5):629-650
The regulation of cardiac Cl- conductance by cAMP-dependent protein kinase (PKA) and cellular phosphatases was studied in isolated guinea pig ventricular myocytes by using wide-tipped, perfused pipettes to record whole-cell currents. Exposure to forskolin (Fsk) or isoproterenol (Iso) elicits a Cl- conductance that results exclusively from PKA-dependent phosphorylation because it can be completely abolished, or its activation fully prevented, by switching to pipette solution containing PKI, a synthetic peptide inhibitor of PKA. The Cl- conductance activated by micromolar concentrations of either agonist reached its steady-state amplitude in 1-2 min and was deactivated promptly and entirely, usually within 2 min, upon washing out the agonist, implying a continuous high level of activity of endogenous protein phosphatases. Accordingly, intracellular application of okadaic acid or microcystin, both potent inhibitors of protein phosphatases 1 and 2A, during exposure to Fsk enhanced the steady-state Cl- conductance and slowed its deactivation after washing out the Fsk. Maximal potentiation of the conductance, by approximately 60%, was obtained with pipette concentrations of approximately 10 microM okadaic acid (or approximately 5 microM microcystin) and did not result from an increase in the apparent affinity for Fsk. In the presence of maximally effective concentrations of okadaic acid and/or microcystin, deactivation of the enhanced Cl- conductance upon washout of agonist was incomplete, with about half of the conductance persisting indefinitely. That residual conductance did not reflect continued action of PKA because it was insensitive to PKI, but was identified as a fraction of the activated Cl- conductance by its biophysical characteristics. The results suggest that complete deactivation of the PKA-regulated cardiac Cl- conductance requires dephosphorylation by a type 1 and/or 2A phosphatase, but that partial deactivation can be accomplished by activity of some other phosphatase(s). These findings are consistent with sequential phosphorylation of a protein, probably the Cl- channel itself, at two different kinds of sites. The resulting phosphoproteins can be distinguished on the basis of their different contributions to whole-cell Cl- conductance. 相似文献
16.
Gaul S Ozsarac N Liu L Fink RH Gage PW 《The Journal of steroid biochemistry and molecular biology》2007,104(1-2):35-44
The effects of the neuroactive steroids alphaxalone and pregnanolone on single GABA(A) receptor channels were tested in cell-attached and inside-out patches from cultured newborn rat hippocampal neurons. The conductance of these single channels ranged between 10 and 80 pS when exposed to low (0.5-3 microM) GABA concentrations. These GABA concentrations activated low-conducting channels (<40 pS) in 78% of the patches, 22% of patches had channels with a maximum conductance above 40 pS. Alphaxalone at concentrations above 1 microM, and pregnanolone at concentrations above 0.1 microM, significantly increased the conductance of initially low-conducting single channels activated by GABA up to seven-fold and at all concentrations tested, both drugs increased open probability and mean open time and decreased closed probability and mean closed time of channels. Both steroids at higher concentrations could directly activate high conductance (>40 pS) chloride channels. Both the directly activated channels and those channels that had been previously affected by alphaxalone were modulated by diazepam, a benzodiazepine drug that is known to specifically modulate GABA(A) channels. The present study is the first one to show that neurosteroids can significantly increase single GABA(A) channel conductance, thus enlarging our current knowledge on the molecular mechanism of action of these compounds. 相似文献
17.
Block of a sarcoplasmic reticulum anion channel (SCl channel) by disulfonic stilbene derivatives [DIDS, dibenzamidostilbene-2,2'-disulfonic acid (DBDS), and 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS)] was investigated in planar bilayers using SO4(2-) as the conducting ion. All molecules caused reversible voltage-dependent channel block when applied to either side of the membrane. DIDS also produced nonreversible channel block from both sides within 1-3 min. Reversible inhibition was associated with a decrease in channel open probability and mean open duration but not with any change in channel conductance. The half inhibitory concentration for cis- and trans-inhibition had voltage dependencies with minima of 190 nM and 33 microM for DBDS and 3.4 and 55 microM for DNDS. Our data supports a permeant blocker mechanism, in which stilbenes block SCl channels by lodging in the permeation pathway, where they may dissociate to either side of the membrane and thus permeate the channel. The stilbenes acted as open channel blockers where the binding of a single molecule occludes the channel. DBDS and DNDS, from opposite sides of the membrane, competed for common sites on the channel. Dissociation rates exhibited biphasic voltage dependence, indicative of two dissociation processes associated with ion movement in opposite directions within the trans-membrane electric field. The kinetics of DNDS and DBDS inhibition predict that there are two stilbene sites in the channel that are separated by 14-24 A and that the pore constriction is approximately 10 A in diameter. 相似文献
18.
The behavior of the mitochondrial inner membrane multiple conductance channel (MCC) which has a peak conductance of 1-1.5 nS has been examined in rat heart mitochondria. MCC can display several unique characteristics: (a) prolonged open and closed times on the order of seconds to minutes, (b) a voltage dependence in which MCC opens (negative potential) or closes (positive potential) generally in steps, (c) a response to inhibitors such as amiodarone in steps corresponding at least approximately to those in (b), (d) a 'free-running mode' in which the current level rapidly fluctuates between a minimum of nine conductance levels but with a preferred occupation of the 0.5-0.7 nS levels, and (e) very large transitions (1-1.5 nS) resolved at 4 kHz bandwidth as single events with variable mean open time. 相似文献
19.
The mitochondrial channel VDAC has a cation-selective open state 总被引:2,自引:0,他引:2
Pavlov E Grigoriev SM Dejean LM Zweihorn CL Mannella CA Kinnally KW 《Biochimica et biophysica acta》2005,1710(2-3):96-102
The mitochondrial channel VDAC is known to have two major classes of functional states, a large conductance "open" state that is anion selective, and lower conductance substates that are cation selective. The channel can reversibly switch between open and half-open states, with the latter predominant at increasing membrane voltages of either polarity. We report the presence of a new functional state of VDAC, a cation-selective state with conductance approximately equal to that of the canonical open state. This newly described state of VDAC can be reached from either the half-open cation-selective state or from the open anion-selective state. The latter transition implies that a mechanism exists for selectivity gating in VDAC that is separate from partial closure, which may be relevant to the physiological regulation of this channel and mitochondrial outer membrane permeability. 相似文献
20.
Gu XQ Siemen D Parvez S Cheng Y Xue J Zhou D Sun X Jonas EA Haddad GG 《Biochemical and biophysical research communications》2007,358(1):311-316
To explore the potential function of the BK channel in the inner mitochondrial membrane under physiological and hypoxic conditions, we used on-mitoplast and whole-mitoplast patches. Single BK channels had a conductance of 276+/-9 pS under symmetrical K(+) solutions, were Ca(2+)- and voltage-dependent and were inhibited by 0.1 microM charybdotoxin. In response to hypoxia, BK increased open probability, shifted its reversal potential (9.3+/-2.4 mV) in the positive direction and did not change its conductance. We conclude that (1) the properties at rest of this mitoplast K(+) channel are similar to those of BK channels in the plasma membrane; (2) hypoxia induces an increase, rather than a decrease (as in the plasmalemma), in the open probability of this K(+) channel, leading to K(+) efflux from the mitochondrial matrix to the outside. We speculate that this increase in K(+) efflux from mitochondria into the cytosol is important during hypoxia in maintaining cytosolic K(+). 相似文献