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1.
With the help of a standard voltage-clamp technique, we investigated transmembrane ion currents in isolated smooth muscle
cells of the guinea pigtaenia coli. In Ca2+-dependent K+ current, we identified and studied the properties of an apamin-sensitive voltage-independent component carried through the
channels of low conductance (in many publications called small conductance,I
SK(Ca)). This component did not show the temporal inactivation;I
SK(Ca) was insensitive to the action of 4 mM tetraethylammonium, but was completely blocked by 500 nM of apamin. It was shown thatI
SK(Ca) is very sensitive to changes in the intracellular Ca2+ concentration ([Ca2+]
i
): a decrease in [Ca2+]
i
up to 50 nM resulted in the almost complete blockade of the current. The entry of Ca ions into a cell from the external solution
through the voltage-operated Ca2+ channels of L-type was not an obligatory condition for activation ofI
SK(Ca). The current-voltage relationship forI
SK(Ca) had a maximum within the voltage range of +20 to +50 mV.
Neirofiziologiya/Neurophysiology, Vol. 32, No. 2, pp. 87–94, March–April, 2000. 相似文献
2.
Bkaily Ghassan Sculptoreanu Adrian Jacques Danielle Jasmin Gaétan 《Molecular and cellular biochemistry》1997,176(1-2):199-204
In the present study, the whole-cell voltage clamp technique was used in order to record the T- and L-type Ca2+ currents in single heart cells of newborn and young normal and hereditary cardiomyopathic hamsters. Our results showed that the I/V relationship curve as well as the kinetics of the L-type Ca2+ currents (ICa(L)) in both normal and cardiomyopathic heart cells were the same. However, the proportion of myocytes from normal heart hamster that showed L-type ICa was less than that of heart cells from cardiomyopathic hamster. The I/V relationship curve of the T-type ICa (ICa(T)) was the same in myocytes of both normal and cardiomyopathic hamsters. The main differences between ICa(T) of cardiomyopathic and normal hamster are a larger window current and the proportion of ventricular myocytes that showed this type of current in cardiomyopathic hamster. The high density of ICa(T) as well as the large window current and proportion of myocytes showing ICa(T) may explain in part Ca2+ overload observed in cardiomyopathic heart cells of the hamster. 相似文献
3.
《Channels (Austin, Tex.)》2013,7(4):361-369
The presence of Ca2+-activated Cl– currents (ICl(Ca)) in vascular smooth muscle cells (VSMCs) is well established. ICl(Ca) are supposedly important for arterial contraction by linking changes in [Ca2+]i and membrane depolarization. Bestrophins and some members of the TMEM16 protein family were recently associated with ICl(Ca). Two distinct ICl(Ca) are characterized in VSMCs; the cGMP-dependent ICl(Ca) dependent upon bestrophin expression and the ‘classical’ Ca2+-activated Cl– current, which is bestrophin-independent. Interestingly, TMEM16A is essential for both the cGMP-dependent and the classical ICl(Ca). Furthermore, TMEM16A has a role in arterial contraction while bestrophins do not. TMEM16A’s role in the contractile response cannot be explained however only by a simple suppression of the depolarization by Cl– channels. It is suggested that TMEM16A expression modulates voltage-gated Ca2+ influx in a voltage-independent manner and recent studies also demonstrate a complex role of TMEM16A in modulating other membrane proteins. 相似文献
4.
Using the voltage-clamp technique, we investigated transmembrane ion currents in isolated smooth muscle cells of the guinea
pigtaenia coli. In our study, we identified and studied a charibdotoxin-sensitive component of Ca2+-dependent K+ current carried through the channels of high conductance (in most publications called “big conductance,”I
BK(Ca)). This component was completely blocked by 100 nM charibdotoxin and by tetraethylammonium in concentrations as low as 1 mM.I
BK(Ca) demonstrated fast kinetics of inactivation, which nearly coincided with that of Ca2+ current. In addition to the dependence on Ca2+ concentration, this current also showed voltage-dependent properties: with a rise in the level of depolarization its amplitude
increased. In many cells, depolarizing shifts in the membrane potential evoke spontaneous outward currents. Such currents
probably represent the secondary effect of cyclic Ca2+ release from the caffeine-sensitive intracellular stores that result in short-term activation of charibdotoxin-sensitive
Ca2+-dependent K+ channels. 相似文献
5.
Nicholas Sperelakis Yoshihito Inoue Yusuke Ohya 《Molecular and cellular biochemistry》1992,114(1-2):79-89
Summary Smooth muscle cells normally do not possess fast Na2+ channels, but inward current is carried through two types of Ca2+ channels: slow (L-type) Ca2+ channels and fast (T-type) Ca2+ channels. Using whole-cell voltage clamp of single smooth muscle cells isolated from the longitudinal layer of 18-day pregnant rat uterus, depolarizing pusles, applied from a holding potential of –90 mV, evoked two types of inward current, fast and slow [8]. The fast inward current decayed within 30 ms, depended on [Na]0, and was inhibited by TTX (K0.5 = 27 nM). The slow inward current decayed slowly, was dependent on [Ca]0, and was inhibited by nifedipine. These results suggest that the fast inward current is a fast Na2+ channel current, and that the slow inward current is a Ca2+ channel current was not evident. Thus, the ion channels which generate inward currents in pregnant rat uterine cells are TTX-sensitive fast Na+ channels and dihudropuridine-sensitive slow Ca2+ channels. The number of fast Na+ channels increased during gestation [9]. The averaged current density increased from 0 on day 5, to 0.19 on day 9, to 0.56 on day 14, to 0.90 on day 18, and to 0.86 pA/pF on day 21. This almost linear increase occurs because of an increase in the fraction of cells which possess fast Na2+ channels, and it suggested that the fast Na+ current may be involved in spread of excitation. The Ca2+ channel current density also was higher during the latter half of gestation. These results indicate that the fast Na+ channels and Ca2+ slow channels in myometrium become more numerous as term approaches, and may facilitate parturition. Isoproterenol (beta-agonist) did not affect either ICa(s) or INa(f), whereas Mg2+ (K0.5 of 12 mM) and nifedipine (K0.5 of 3.3 nM) depressed ICa(s). Oxytocin had no effect on INa(f) and actually depressed ICa(s) to a small extect. Therefore, the tocolytic action of beta-agonists cannot be explained by an inhibition of ICa(s), whereas that of Mg2+ can be so explained. The stimulating action of oxytocin on uterine contractions is not due to stimulation of ICa(s). 相似文献
6.
To clarify the transmural heterogeneity of action potential (AP) time course, we examined the regulation of L-type Ca2+ current (ICa,L) by voltage and Ca2+-dependent mechanisms. Currents were recorded using patch clamp of single rat subepicardial (EPI) and subendocardial (ENDO) of left ventricular, right ventricular (RV) and septal (SEP) cardiomyocytes. Voltage clamp commands were derived from ENDO and EPI APs or rectangular voltage pulses.During rectangular pulses, peak ICa,L was significantly greater in EPI than in other cells. The inactivation of ICa,L by Ca2+-dependent mechanisms (suppressed by ryanodine and BAPTA) was present in all cells but greater in extent in ENDO and SEP cells. Activation and inactivation curves for all regions show subtle differences that are Ca2+ sensitive, with Ca2+ inactivation shifting the activation variables negative by ∼ 7 mV and inactivation variables positive by 2-7 mV (EPI being least, RV greatest). In AP-clamps, the peak ICa,L was significantly smaller in ENDO than in EPI cells, while the integrated current was significantly larger in ENDO than in EPI cells. The results are discussed with regard to the interplay of AP time course and net Ca2+ influx. 相似文献
7.
Summary The action of GRF on GH3 cell membrane was examined by patch electrode techniques. Under current clamp with patch elecrtrode, spontaneous action potentials were partially to totally eliminated by application of GRF. In the case of partial elimination, the duration of remaining spontaneous action potentials was prolonged and the amplitude of afterhyperpolarization was decreased. The evoked actiion potential in the cells which did not show spontaneous action potentials was also eliminated by GRF. In order to examine what channels were affected by GRF, voltage-clamp analysis was performed. It was revealed that voltage-gated Ca2+ channel current and Ca2+-induced K+ channels current were decreased by GRF, while voltage-gated Na+ channel and delayed K+ channel current was considered to be a consequence of he decrease of voltage-gated Ca2+ channels current. Therefore it is likely that the effect of GRF on GH3 cells was due to the block of voltage-gated Ca2+ channels. The elimination of action potential under current clamp corresponded to the block of voltage-gated Ca2+ channels and the prolongation of action potential could be explained by the decrease of Ca2+-induced K+ channel current. The amplitude decrease of afterhyperpolarization could also be explained by the reduction of Ca2+-induced K+ channel current. Thus the results under current clamp well coincide with the results under voltage clamp. Hormone secretion from GH3 cells was not stimulated by GRF. However, the finding that GRF solely blocked voltage-gated Ca2+ channel suggested the specific action of GRF on GH3 cell membranes. 相似文献
8.
Vibeke Secher Dam Donna MB Boedtkjer Christian Aalkjaer Vladimir Matchkov 《Channels (Austin, Tex.)》2014,8(4):361-369
The presence of Ca2+-activated Cl– currents (ICl(Ca)) in vascular smooth muscle cells (VSMCs) is well established. ICl(Ca) are supposedly important for arterial contraction by linking changes in [Ca2+]i and membrane depolarization. Bestrophins and some members of the TMEM16 protein family were recently associated with ICl(Ca). Two distinct ICl(Ca) are characterized in VSMCs; the cGMP-dependent ICl(Ca) dependent upon bestrophin expression and the ‘classical’ Ca2+-activated Cl– current, which is bestrophin-independent. Interestingly, TMEM16A is essential for both the cGMP-dependent and the classical ICl(Ca). Furthermore, TMEM16A has a role in arterial contraction while bestrophins do not. TMEM16A’s role in the contractile response cannot be explained however only by a simple suppression of the depolarization by Cl– channels. It is suggested that TMEM16A expression modulates voltage-gated Ca2+ influx in a voltage-independent manner and recent studies also demonstrate a complex role of TMEM16A in modulating other membrane proteins. 相似文献
9.
Cardiac fibroblasts are involved in the maintenance of myocardial tissue structure. However, little is known about ion currents
in human cardiac fibroblasts. It has been recently reported that cardiac fibroblasts can interact electrically with cardiomyocytes
through gap junctions. Ca2+-activated K+ currents (I
K[Ca]) of cultured human cardiac fibroblasts were characterized in this study. In whole-cell configuration, depolarizing pulses
evoked I
K(Ca) in an outward rectification in these cells, the amplitude of which was suppressed by paxilline (1 μM) or iberiotoxin (200 nM). A large-conductance, Ca2+-activated K+ (BKCa) channel with single-channel conductance of 162 ± 8 pS was also observed in human cardiac fibroblasts. Western blot analysis
revealed the presence of α-subunit of BKCa channels. The dynamic Luo-Rudy model was applied to predict cell behavior during direct electrical coupling of cardiomyocytes
and cardiac fibroblasts. In the simulation, electrically coupled cardiac fibroblasts also exhibited action potential; however,
they were electrically inert with no gap-junctional coupling. The simulation predicts that changes in gap junction coupling
conductance can influence the configuration of cardiac action potential and cardiomyocyte excitability. I
k(Ca) can be elicited by simulated action potential waveforms of cardiac fibroblasts when they are electrically coupled to cardiomyocytes.
This study demonstrates that a BKCa channel is functionally expressed in human cardiac fibroblasts. The activity of these BKCa channels present in human cardiac fibroblasts may contribute to the functional activities of heart cells through transfer
of electrical signals between these two cell types. 相似文献
10.
UV irradiation has multiple effects on mammalian cells, including modification of ion channel function. The present study
was undertaken to investigate the response of membrane currents in guinea-pig ventricular myocytes to the type A (355, 380
nm) irradiation commonly used in Ca2+ imaging studies. Myocytes configured for whole-cell voltage clamp were generally held at −80 mV, dialyzed with K+-, Na+-free pipette solution, and bathed with K+-free Tyrode’s solution at 22°C. During experiments that lasted for ≈ 35 min, UVA irradiation caused a progressive increase
in slowly-inactivating inward current elicited by 200-ms depolarizations from −80 to −40 mV, but had little effect on background
current or on L-type Ca2+ current. Trials with depolarized holding potential, Ca2+ channel blockers, and tetrodotoxin (TTX) established that the current induced by irradiation was late (slowly-inactivating)
Na+ current (INa). The amplitude of the late inward current sensitive to 100 μM TTX was increased by 3.5-fold after 20–30 min of irradiation. UVA modulation of late INa may (i) interfere with imaging studies, and (ii) provide a paradigm for investigation of intracellular factors likely to
influence slow inactivation of cardiac INa. 相似文献
11.
Ca2+ store depletion activates both Ca2+ selective and non-selective currents in endothelial cells. Recently, considerable progress has been made in understanding the molecular make-up and regulation of an endothelial cell thapsigargin-activated Ca2+ selective current, ISOC. Indeed, ISOC is a relatively small inward Ca2+ current that exhibits an approximate +40 mV reversal potential and is strongly inwardly rectifying. This current is sensitive to organization of the actin-based cytoskeleton. Transient receptor potential (TRP) proteins 1 and 4 (TRPC1 and TRPC4, respectively) each contribute to the molecular basis of ISOC, although it is TRPC4 that appears to be tethered to the cytoskeleton through a dynamic interaction with protein 4.1. Activation of ISOC requires association between protein 4.1 and the actin-based cytoskeleton (mediated through spectrin), suggesting protein 4.1 mediates the physical communication between Ca2+ store depletion and channel activation. Thus, at present findings indicate a TRPC4–protein 4.1 physical linkage regulates ISOC activation following Ca2+ store depletion. 相似文献
12.
Excitatory effect of ATP on rat area postrema neurons 总被引:1,自引:0,他引:1
ATP-induced inward currents and increases in the cytosolic Ca2+ concentration ([Ca]in) were investigated in neurons acutely dissociated from rat area postrema using whole-cell patch-clamp recordings and fura-2 microfluorometry, respectively. The ATP-induced current (I
ATP) and [Ca]in increases were mimicked by 2-methylthio-ATP and ATP-γS, and were inhibited by P2X receptor (P2XR) antagonists. The current–voltage relationship of the I
ATP exhibited a strong inward rectification, and the amplitude of the I
ATP was concentration-dependent. The I
ATP was markedly reduced in the absence of external Na+, and the addition of Ca2+ to Na+-free saline increased the I
ATP. ATP did not increase [Ca]in in the absence of external Ca2+, and Ca2+ channel antagonists partially inhibited the ATP-induced [Ca]in increase, indicating that ATP increases [Ca]in by Ca2+ influx through both P2XR channels and voltage-dependent Ca2+ channels. There was a negative interaction between P2XR- and nicotinic ACh receptor (nAChR)-channels, which depended on the amplitude and direction of current flow through either channel. Current occlusion was observed at V
hs between −70 and −10 mV when the I
ATP and ACh-induced current (I
ACh) were inward, but no occlusion was observed when these currents were outward at a V
h of +40 mV. The I
ATP was not inhibited by co-application of ACh when the I
ACh was markedly decreased either by removal of permeant cations, by setting V
h close to the equilibrium potential of I
ACh, or by the addition of d-tubocurarine or serotonin. These results suggest that the inhibitory interaction is attributable to inward current flow of cations through the activated P2XR- and nAChR-channels. 相似文献
13.
Summary Glucose-induced electrical activity in canine pancreatic islet B cells is distinct from that in rodent islets, though both display Ca2+-dependent insulin secretion. Rodent islet B cells undergo regular bursts of Ca2+-dependent action potentials, while canine islet B cells generate isolated Na+-dependent action potentials which often give way to a plateau depolarization. Here we present evidence to reconcile the species difference in electrical activity with the similarity of Ca2+ dependence of secretion. (i) In canine B cells increasing glucose concentrations produce membrane depolarization and increasing frequency of Nao-dependent action potentials until a background membrane potential (-40mV) is reached where Na+ currents are inactivated. (ii) Voltage-dependent Ca2+ currents are present which are activated over the voltage excursion of the action potential (–50 to +20 mV) and inactivate slowly, (over seconds) in the range of the plateau depolarization (–40 to –25 mV). Hence, they are available to contribute to both phases of depolarization. (iii) Tetrodotoxin (TTX) reduces by half an early transient phase of glucosestimulated insulin secretion but not a subsequent prolonged plateau phase. The transient phase of secretion often corresponds well in time to the period of initial high frequency action potential activity. These latter results suggest that in canine B cells voltagedependent Na+ and Ca2+ currents mediate biphasic glucose-induced insulin secretion. The early train of Na+-dependent action potentials, by transiently activating Ca2+ channels and allowing pulsatile Ca2+ entry, may promote an early transient phase of insulin secretion. The subsequent sustained plateau depolarization, by allowing sustained Ca2+ entry, may permit steady insulin release. 相似文献
14.
Sammy A. Mason 《Biochemical and biophysical research communications》2009,388(3):565-27593
Adult women have longer QT intervals compared with men of a similar age, indicating differences in the speed of repolarisation of the ventricles. We investigate the influences of gender on ventricular electrophysiology and intracellular Ca2+ regulation of the guinea pig heart. Comparing sexually mature animals, females exhibited a significantly longer APD. Peak L-type Ca2+ current (ICaL) was larger in females and when this current was inhibited with nifedipine the gender differences in APD were removed. APD differences also disappeared when the SR was depleted of Ca2+. Inactivation of ICaL during a clamp step is faster in females but slower during an action potential and SR Ca2+ content is larger. We suggest that gender differences in APD result from variation in the kinetics of ICaL stemming from alterations to Ca2+ release. 相似文献
15.
Summary A new mutant ofParamecium tetraurelia, k-shyA, was characterized behaviorally and electrophysiologically. The mutant cell exhibited prolonged backward swimming episodes in response to depolarizing conditions. Electrophysiological comparison of k-shyA with wild type cells under voltage clamp revealed that the properties of three Ca2+-regulated currents were altered in the mutant. (i) The voltage-dependent Ca2+ current recovered from Ca2+-dependent inactivation two- to 10-fold more slowly than wild type. Ca2+ current amplitudes were also reduced in the mutant, but could be restored by EGTA injection. (ii) The decay of the Ca2+-dependent K+ tail current was slower in the mutant. (iii) The decay of the Ca2+-dependent Na+ tail current was also slower in the mutant. All other membrane properties studied, including the resting membrane potential and resistance and the voltage-sensitive K+ currents, were normal in k-shyA. Considered together, these observations are consistent with a defect in the ability of k-shyA to reduce the free intracellular Ca2+ concentration following stimulation. The possible targets of the genetic lesion and alternative explanations are discussed. The k-shy mutants may provide a useful tool for molecular and physiological analyses of the regulation of Ca2+ metabolism inParamecium. 相似文献
16.
Summary The voltage- and time-dependent K+ current,I
K
+
out
, elicited by depolarization of corn protoplasts, was inhibited by the addition of calcium channel antagonists (nitrendipine, nifedipine, verapamil, methoxyverapamil, bepridil, but not La3+) to the extracellular medium. These results suggested that the influx of external Ca2+ was necessary for K+ current activation. The IC50, concentration of inhibitor that caused 50% reduction of the current, for nitrendipine was 1 m at a test potential of +60 mV following a 20-min incubation period.In order to test whether intracellular Ca2+ actuated the K+ current, we altered either the Ca2+ buffering capacity or the free Ca2+ concentration of the intracellular medium (pipette filling solution). By these means,I
K
+
out
could be varied over a 10-fold range. Increasing the free Ca2+ concentration from 40 to 400nm also shifted the activation of the K+ current toward more negative potentials. Maintaining cytoplasmic Ca2+ at 500nm with 40nm EGTA resulted in a more rapid activation of the K+ current. Thus the normal rate of activation of this current may reflect changes in cytoplasmic Ca2+ on depolarization. Increasing intracellular Ca2+ to 500nm or 1 m also led to inactivation of the K+ current within a few minutes. It is concluded thatI
K
+
out
is regulated by cytosolic Ca2+, which is in turn controlled by Ca2+ influx through dihydropyridine-, and phenylalkylamine-sensitive channels. 相似文献
17.
Young-Hwan Kim Taick-Sang Nam Duck-Sun Ahn Seungsoo Chung 《Biochemical and biophysical research communications》2011,(4):645
Moxonidine, an imidazoline deriviatives, suppress the vasopressor sympathetic outflow to produce hypotension. This effect has been known to be mediated in part by suppressing sympathetic outflow via acting imidazoline I1 receptors (IR1) at postganglionic sympathetic neurons. But, the cellular mechanism of IR1-induced inhibition of noradrenaline (NA) release is still unknown. We therefore, investigated the effect of IR1 activation on voltage-dependent Ca2+ channels which is known to play an pivotal role in regulating NA in rat superior cervical ganglion (SCG) neurons, using the conventional whole-cell patch-clamp method. In the presence of rauwolscine (3 μΜ), which blocks α2-adrenoceptor (Rα2), moxonidine inhibited voltage-dependent Ca2+ current (ICa) by about 30%. This moxonidine-induced inhibition was almost completely prevented by efaroxan (10 μΜ) which blocks IR1 as well as Rα2. In addition, ω-conotoxin (CgTx) GVIA (1 μΜ) occluded moxonidine-induced inhibition of ICa, but, moxonidine-induced ICa inhibition was not affected by pertussis toxin (PTX) nor shows any characteristics of voltage-dependent inhibition. These data suggest that moxonidine inhibit voltage-dependent N-type Ca2+ current (ICa–N) via activating IR1. Finally, moxonidine significantly decreased the frequency of AP firing in a partially reversible manner. This inhibition of AP firing was almost completely occluded in the presence of ω-CgTx. Taken together, our results suggest that activation of IR1 in SCG neurons reduced ICa–N in a PTX-and voltage-insensitive pathway, and this inhibition attenuated repetitive AP firing in SCG neurons. 相似文献
18.
Mutoh H Yoshino M 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2004,174(1):21-28
The Ca2+-conducting pathway of myocytes isolated from the cricket lateral oviduct was investigated by means of the whole-cell patch clamp technique. In voltage-clamp configuration, two types of whole cell inward currents were identified. One was voltage-dependent, initially activated at –40 mV and reaching a maximum at 10 mV with the use of 140 mM Cs2+-aspartate in the patch pipette and normal saline in the bath solution. Replacement of the external Ca2+ with Ba2+ slowed the current decay. Increasing the external Ca2+ or Ba2+ concentration increased the amplitude of the inward current and the current–voltage (I–V) relationship was shifted as expected from a screening effect on negative surface charges. The inward current could be carried by Na+ in the absence of extracellular Ca2+. Current carried by Na+ (I
Na) was almost completely blocked by the dihydropyridine Ca2+ channel antagonist, nifedipine, suggesting that the I
Na is through voltage-dependent L-type Ca2+ channels. The other inward current is voltage-independent and its I–V relationship was linear between –100 mV to 0 mV with a slight inward rectification at more hyperpolarizing membrane potentials when 140 mM Cs+-aspartate and 140 mM Na+-gluconate were used in the patch pipette and in the bath solution, respectively. A similar current was observed even when the external Na+ was replaced with an equimolar amount of K+ or Cs+, or 50 mM Ca2+ or Ba2+. When the osmolarity of the bath solution was reduced by removing mannitol from the bath solution, the inward current became larger at negative potentials. The I–V relationship for the current evoked by the hypotonic solution also showed a linear relationship between –100 mV to 0 mV. Bath application of Gd3+ (10 M) decreased the inward current activated by membrane hyperpolarization. These results clearly indicate that the majority of current activated by a membrane hyperpolarization is through a stretch-activated Ca2+-permeable nonselective cation channel (NSCC). Here, for the first time, we have identified voltage-dependent L-type Ca2+ channel and stretch-activated Ca2+-permeable NSCCs from enzymatically isolated muscle cells of the cricket using the whole-cell patch clamp recording technique.Abbreviations
I
Ca
Ca2+ current
-
I
Na
Na+ current
-
I–V
current–voltage
-
NSCC
nonselective cation channel
Communicated by G. Heldmaier 相似文献
19.
S. L. Mironov 《The Journal of membrane biology》1994,141(3):231-237
The effect of amidiniums on high-threshold Ca2+ channel currents (I
Ca) was studied in chick dorsal root ganglion neurons. Guanidinium reduced I
Ca in a dose-dependent fashion. The block was relieved by increasing the concentration of the permeant ions, Ba2+ or Ca2+, suggesting a competition for a common binding site within the channel. Formamidinium and methyl-guanidinium suppressed I
Ca with similar potencies, whereas l-arginine had no effect. A neutral amidine, urea, increased I
Ca. In Ca2+-free solutions guanidinium and Na+ permeated through the Ca2+ channel equally well. Structure-activity relationship obtained for blocking efficacies of different amidiniums are used to discuss possible configurations of the selectivity filter in the Ca2+ channel.The author wishes to thank Ms. S. Engers for the cell isolation and making of the electrodes. 相似文献
20.
Nicholas Sperelakis Zhiling Xiong G. Haddad Hiroshi Masuda 《Molecular and cellular biochemistry》1994,140(2):103-117
The slow Ca2+ channels (L-type) of the heart are stimulated by cAMP. Elevation of cAMP produces a very rapid increase in number of slow channels available for voltage activation during excitation. The probability of a Ca2+ channel opening and the mean open time of the channel are increased. Therefore, any agent that increases the cAMP level of the myocardial cell will tend to potentiate ICa, Ca2+ influx, and contraction. The action of cAMP is mediated by PK-A and phosphorylation of the slow Ca2+ channel protein or an associated regulatory protein (stimulatory type). The myocardial slow Ca2+ channels are also rogulated by cGMP, in a manner that is opposite orantagonistic to that of cAMP. We have demonstrated this at both the macroscople level (whole-cell voltage clamp) and the single-channel level. The effect of cGMP is mediated by PK-G and phosphorylation of a protein, as for example, a regulatory protein (inhibitory-type) associated with the Ca2+ channel. Introduction of PK-G intracellularly causes a relatively rapid inhibition of ICa(L) in both chick and rat heart cells. Such inhibition occurs for both the basal and stimulated ICa(L). In addition, the cGMP/PK-G system was reported to stimulate a phosphatase that dephosphorylates the Ca2+ channel. In addition to the slower indirect pathway—exerted via cAMP/PK-A—there is a faster more-direct pathway for ICa(L) stimulation by the -adrenergic receptor. This latter pathway involves direct modulation of the channel activity by the alpha subunit (s*) of the Gs-protein. In vascular smooth muscle cells the two pathways (direct and indirect) also appear to be present, although the indirect pathway producesinhibition of ICa(L). PK-C and calmodulin-PK also may play roles in regulation of the myocardial slow Ca2+ channels. Both of these protein kinases stimulate the activity of these channels. Thus, it appears that the slow Ca2+ channel is a complex structure, including perhaps several associated regulatory proteins, which can be regulated by a number of factors intrinsic and extrinsic to the cell, and thereby control can be exercised over the force of contraction of the heart.This review-type article was prepared by modifying an article published in a book by Sperelakiset al., 1994. 相似文献