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Results for “Calcium Channels, T-Type”

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PubMed1992

Ca2+ currents in single myocytes from human mesenteric arteries: evidence for a physiological role of L-type channels.

1. Voltage-gated Ca2+ currents (ICa) in isolated human mesenteric arterial cells were characterized in solutions containing normal (1.5 mM) Ca2+ and elevated concentrations of divalent cations using the conventional whole-cell patch clamp technique. 2. In normal Ca2+ solution, depolarization beyond -40 mV elicited a slowly decaying ICa which reached a maximum at +10 mV and appeared to reverse between +40 and +50 mV. The amplitude of this current in a group of cells correlated with cell membrane capacitance. 3. In two of thirty-three cells a small transient component of inward current was detected in the voltage range between -40 and -10 mV when cells were held at -80 mV. This current was abolished at a holding potential of -40 mV, while the current at 10 mV was not affected. These currents were referred to as T- and L-type Ca2+ respectively. 4. Elevation of the extracellular Ca2+ concentration to 20 mM shifted the voltage dependencies of Ca2+ current activation and inactivation by approximately +20 mV; a small T-current component was then observed in seven of nine cells held at -60 mV. 5. Replacement of 1.5 mM Ca2+ with 10 mM Ba2+ increased the amplitude of the current elicited at +10 mV by a factor of 3.7 and a small barium current (IBa) through T-type Ca2+ channels was also observed in most cells studied. Activation and steady-state inactivation curves for L-type current were found to be almost identical in both solutions. The steady-state inactivation for the T-type IBa was, however, more than 30 mV more negative (half-inactivation potential of -62.6 mV) of that for L-current in 1.5 mM Ca2+ and 10 mM Ba2+ solutions (-30.4 and -24.9 mV respectively). 6. A sustained inward Ca2+ channel current was recorded in the presence of normal Ca2+ and high divalent cation concentrations during 30 s depolarizations. The amplitude of this sustained current was found to be similar to the theoretical 'window current' predicted by the overlap of the activation and inactivation functions in these solutions. 7. Examination of the inactivation of the L-type current using a two-pulse protocol with a 240 ms prepulse revealed a U-shaped potential dependency for ICa, but not for IBa, suggesting the presence of a Ca(2+)-dependent component of the inactivation process. 8. These cells resemble other arterial smooth muscle cells previously studied in that they demonstrate both T- and L-components of ICa.(ABSTRACT TRUNCATED AT 400 WORDS)

Barium↗

PubMed1992

Voltage-dependent ionic currents in dissociated paratracheal ganglion cells of the rat.

1. Conventional whole-cell voltage-clamp technique was used to study the electrophysiological and pharmacological properties of voltage-dependent Na+, K+ and Ca2+ channels in parasympathetic neurones enzymatically dissociated from the paratracheal ganglia of rat trachea. The voltage-dependent Na+, K+ and Ca2+ currents (INa, IK and ICa) were separated by the use of ion subtraction and pharmacological treatments. 2. INa was activated by a step depolarization more positive than -50 mV and fully activated at positive potentials more than +10 mV. The inactivation phase of INa consisted of fast and slow exponential components (tau if and tau is, respectively). The tau if and tau is were voltage dependent and decreased with a more positive step pulse. 3. The time course for recovery of INa from the complete inactivation exhibited two exponential processes. 4. The reversal potential of INa was equal to the Na+ equilibrium potential (ENa) and resembled a simple Na+ electrode depending only on external Na+ concentration. 5. Tetrodotoxin (TTX) reduced INa without affecting the current kinetics in a concentration-dependent manner, and the concentration of half-maximal inhibition (IC50) was 6 x 10(-9) M. There was no TTX-resistant component of INa in any of the cells tested. 6. Scorpion toxin increased the peak amplitude of INa and prolonged the inactivation phase in a time- and concentration-dependent manner. In the presence of toxin, both tau is and the fractional contribution of the slow current component to total INa increased concentration dependently. 7. High-threshold (L-type) ICa was activated by a step depolarization more positive than -30 mV and reached a peak at near 0 mV in the external solution with 2.5 mM Ca2+. The current was inactivated to only a small extent (< 10%) during 100 ms of depolarizing step pulse. There was no low-threshold (T-type) ICa in this preparation. 8. The maximum ICa in individual current-voltage (I-V) relationships was saturated by an increase in extracellular Ca2+ concentration ([Ca2+]o). The I-V relationships were also shifted along the voltage axis to the more positive potential with increasing [Ca2+]o. 9. The inactivation process of the L-type ICa was dependent on Ca2+ influxes (ICa-dependent inactivation). 10. Relative maximum peak currents of divalent cations passing through the L-type Ca2+ channels were in the order of IBa > ICa > ISr. 11. Organic and inorganic Ca2+ antagonists blocked the ICa in a concentration-dependent manner.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Gadolinium blocks low- and high-threshold calcium currents in pituitary cells.

The inhibition of L- and T-type Ca2+ currents by Gd3+ was studied in the rat pituitary GH4C1 cell line. In whole cell patch recordings, Gd3+ at concentrations of 50 nM to 5 microM blocked Ca2+ current through L-type channels. Block was promoted by prolonged channel activation. With 4.5-s test pulses to + 10 mV, Gd3+ at concentrations as low as 200 nM produced near-complete block of L current. At higher Gd3+ concentrations (5 microM), complete block occurred with short test pulses and appeared to be independent of channel activation. Gd3+ also blocked current through low-threshold T channels in GH4C1 cells. Two other trivalent elements, La3+ and Y3+, blocked L-type Ca2+ channels in GH4C1 cells with potency similar to Gd3+. These results indicate that these trivalent cations are effective nonselective inhibitors of both low- and high-threshold Ca2+ channels in endocrine cells. In this regard, they are among the most potent inorganic Ca2+ antagonists yet discovered.

Animals↗

PubMed1991

Multiple calcium currents in a thyroid C-cell line: biophysical properties and pharmacology.

The whole cell version of the patch-clamp technique was used to characterize voltage-gated Ca2+ channels in the calcitonin-secreting rat thyroid C-cell line 6-23 (clone 6). Three types of Ca2+ channels could be distinguished based on differences in voltage dependence, kinetics, and pharmacological sensitivity. T-type current was half-maximal at -31 mV, showed steady-state voltage-dependent inactivation that was half-maximal at -57 mV, inactivated with a voltage-dependent time constant that reached a minimum of 20 ms at potentials positive to -20 mV, and deactivated with a single time constant of approximately 2 ms at -80 mV. Reactivation of inactivated channels occurred with a time constant of 1.26 s at -90 mV. T current was selectively blocked by Ni2+ at concentrations between 5 and 50 microM. La3+ and Y3+ blocked the T current at 10- to 20-fold lower concentrations. Dihydropyridine-sensitive L-type current was half-maximal at a test potential of -3 mV and was approximately doubled in size when Ba2+ replaced Ca2+ as the charge carrier. Unlike L-type Ca2+ current in many cells, this current in C-cells displayed little Ca(2+)-dependent inactivation. N-type current was composed of inactivating and sustained components that were inhibited by omega-conotoxin. The inactivating component was half-maximal at +9 mV and could be fitted by two exponentials with time constants of 22 and 142 ms. A slow inactivation of N current with a time constant of 24.9 s was observed upon switching the holding potential from -80 to -40 mV. These results demonstrate that, similar to other neural crest derived cells, thyroid C-cells express multiple Ca2+ channels, including one previously observed only in neurons.

Animals↗

PubMed1991

Ca2+ current and Ca2+ transients under action potential clamp in guinea pig ventricular myocytes.

Precise characterization of the magnitude and kinetics of transsarcolemmal Ca2+ influx during an action potential (AP) is essential for a complete understanding of excitation-contraction coupling in heart. Using a voltage-clamp protocol that simulated a physiological AP (AP clamp), we characterized the properties of the Ca2+ current (ICa) in guinea pig ventricular myocytes. The AP-generated ICa showed a complex time course that was different from ICa generated by a square pulse. ICa activated rapidly during the upstroke of the AP and then partially inactivated during the plateau. The fast component of ICa reached a peak value of -7.6 +/- 1.0 pA/pF at 2.40 +/- 0.30 ms after depolarization, followed by a slow component with a peak value of -2.9 +/- 0.4 pA/pF during the plateau. ICa generated by an AP was composed of both L- and T-type Ca2+ channels. T-type Ca2+ current contributed to the fast component of ICa and L-type Ca2+ current contributed to both fast and slow components of ICa. Activation of beta-adrenoceptors enhanced ICa with a maximal effect lasting throughout the entire plateau of the AP. Measurements of cytosolic Ca2+ transients using fura-2 indicated that the ICa was responsible for triggering Ca2+ release from the sarcoplasmic reticulum. The AP clamp provides a new approach for investigation of the relationship between ICa and Ca2+ transients under more physiological conditions.

Action Potentials↗

PubMed1992

Apamin, a highly potent fetal L-type Ca2+ current blocker in single heart cells.

Apamin, a bee venom polypeptide, was reported to block the naturally occurring Ca2+ slow action potentials (APs) in cultured cell reaggregates from old chick hearts [Bkaily, G. et al. Am. J. Physiol. 248 (Heart Circ. Physiol. 17): H961-H965, 1985] as well as the tetrodotoxin (TTX)- and Mn(2+)-insensitive slow Na+ current in young embryonic chick heart cells (Bkaily, G. In Vitro Toxicology. Academic, In press; Bkaily et al. J. Mol. Cell. Cardiol. 23: 25-39, 1991). With the use of the whole cell voltage-clamp technique in single ventricular cells from 10-day-old chick embryos and 17- to 20-wk-old human fetuses, two types of Ca2+ currents (ICa), T and L, were found. These two types of slow inward current in both heart preparations were nearly similar in their voltage, kinetics, and pharmacology. Apamin, a slow Ca2+ action potential blocker in old embryonic chick heart, was found to block the L-type ICa (IL) in a dose-dependent manner without affecting the T-type ICa in both heart cell preparations. The blockade of the IL by apamin was completely reversible upon washout with apamin-free solution. Therefore, when compared with nifedipine or to PN 200-110, apamin seems to be a highly potent L-type Ca2+ channel blocker in heart cells.

Animals↗

PubMed1992

Calcium currents in hearts with persistent truncus arteriosus.

We have used the neural crest model of defective heart development to characterize both L- and T-type Ca2+ currents (ICa,L and ICa,T) in ventricular myocytes from embryonic chick hearts with a severe outflow tract anomaly known as persistent truncus arteriosus (PTA). Because of smaller whole embryo weights but no significant change in the weights of ventricles with PTA, the ventricle to whole embryo weight ratios from hearts with PTA were 61% larger than normal at day 11 of incubation. There was a 51% reduction in the peak magnitude of ICa,L at a test potential of +10 mV (-1.4 vs. -0.7 microA/cm2), whereas ICa,T, a proportionately large fraction of the total Ca2+ current in the embryonic chick ventricle, was unaffected. In comparison to sham-operated controls, ICa,L was otherwise not different. Half-activation occurred at about -1 and -41 mV, whereas half-inactivation occurred at -19 and -61 mV for ICa,L and ICa,T, respectively. The time for half-recovery from inactivation were not different and were 200 and 230 ms for ICa,L and ICa,T, respectively. The time for half-decay of the currents and their responses to BAY K 8644 were also similar in both sham-operated and experimental hearts. Although the dihydropyridine receptor binding experiments suggest that the total number of L-type Ca2+ channels was not different, the results from the physiological experiments indicate that the number of functional L-type channels available for opening and/or the single-channel conductance may be reduced in hearts with PTA. Finally, our results with the neural crest model indicate that it is unlikely that the development of Ca2+ currents is influenced by the onset of cholinergic innervation in the heart.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1991

Ca2+ channels and aldosterone secretion: modulation by K+ and atrial natriuretic peptide.

Two populations of voltage-dependent Ca2+ channels, T-type and L-type, are present in bovine adrenal glomerulosa cells. Activation of these channels by cell depolarization with the resultant increase in Ca2+ influx may be one way in which agonists regulate aldosterone secretion. In addition, these channels may be the site of antagonist action. In the present study, we have demonstrated that atrial natriuretic peptide (ANP), an antagonist of aldosterone secretion, alters only the voltage dependence of inactivation of the T-type channel while enhancing the voltage dependence of activation of a subpopulation of L-type channels. These patch-clamp data, which demonstrated contrasting effects of ANP on the activity of T- and L-type Ca2+ channels correlated with changes induced in cytosolic calcium [( Ca2+]i). In the weakly depolarized cell, ANP (greater than 30 pM) lowered [Ca2+]i, in contrast to the strongly depolarized cell, in which ANP (greater than 10 pM) raised [Ca2+]i. Similar alterations in the level of [Ca2+]i in the stimulated cell were induced by the Ca(2+)-channel blocker nitrendipine and the L-type channel agonist, (-)BAY K 8644. With increasing concentrations of extracellular K+ (3.5-60 mM) the rate of aldosterone secretion rose nonmonotonically. ANP inhibited secretion over this broad range of K+ concentrations; however, its potency as an inhibitor of secretion was diminished in the strongly depolarized cell. These data are discussed in the context of a model that proposes a role for sustained Ca2+ influx in cell activation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1990

Low-threshold calcium current in isolated Purkinje cell bodies of rat cerebellum.

1. The low- and high-threshold Ca2+ currents were observed in Purkinje cell bodies isolated from the cerebellum of newborn (2 wk old) and adult (8 wk old) rats under whole-cell clamp. A transient Ca2+ current (low-threshold or "T-type" ICa) was elicited by depolarizing step pulses to -60 mV or more positive potentials from a holding potential (VH) of -100 mV. In cells dissociated from newborn rats, a long-lasting Ca2+ current (high-threshold or "L-type" ICa) was also elicited by depolarizing command pulses beyond -30 mV. 2. The low-threshold ICa was resistant to the "washout" effect during the internal perfusion, whereas the high-threshold ICa faded gradually with time during the continuous internal perfusion. 3. In the current-voltage (I-V) relationship, the low-threshold ICa had a threshold potential around -60 mV and reached the maximum inward current around -20 mV. The activation and inactivation kinetics of the current depended on membrane potential: for a test-potential change from -60 to +40 mV, the time to peak of the current (activation) decreased from 31.9 to 5.0 ms, and the time constant of current decay (inactivation) decreased from 78.5 to 22.9 ms. 4. Steady-state inactivation of low-threshold ICa was membrane-potential dependent, and the inactivation of the 50% level was -79 mV. Recovery time constant from steady-state inactivation varied depending on the membrane potential. The time constants were 3.3 and 2.5 s at VHs of -100 and -120 mV, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Reduced L-type calcium current in the embryonic chick heart with persistent truncus arteriosus.

Calcium currents were examined in an experimental model in the embryonic chick heart with a congenital malformation known as persistent truncus arteriosus. This is a severe defect characterized by failure of conotruncal and aorticopulmonary septation of the embryonic heart tube. As a result, no separation into the aortic and pulmonary arteries occurs, and there is a common outflow tract. The hearts with persistent truncus arteriosus had a 26% greater ventricular to whole embryo weight, which indicated that the ventricles were enlarged. Both the low-threshold T-type (ICa.T) and the 1,4-dihydropyridine-sensitive L-type (ICa.L) Ca2+ currents were present in the ventricular myocytes from hearts at day 11 of incubation. However, day 11 hearts with persistent truncus arteriosus showed a twofold reduction in the peak magnitude of ICa.L at a test potential of + 10 mV without a concomitant reduction in the number of L channels detected by 1,4-dihydropyridine antagonist [(+)[3H]PN200-110] and agonist (Bay K 8644) receptor binding. The results indicated that an L channel regulatory mechanism other than protein synthesis was affected. These changes are consistent with responses to conditions of excessive hemodynamic burden that have been characterized in adult hearts.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1990

Actions of Ca2+ antagonists on two types of Ca2+ channels in rat aorta smooth muscle cells in primary culture.

Mechanisms of blockade of two types of Ca2+ channels by the organic Ca2+ antagonists, nicardipine, diltiazem, verapamil, and flunarizine, were examined in rat aorta smooth muscle cells in primary culture by using the whole-cell voltage-clamp method. T-type Ca2+ current (T-type ICa) was isolated by an internal perfusion of 5 mM F-, which irreversibly suppressed the L-type ICa, without affecting T-type ICa. L-type ICa was isolated by setting a holding potential at -60 mV, at which most of the T-type Ca2+ channels were inactivated. L-type ICa is halved by 0.1 microM nicardipine, 3.0 microM diltiazem, 0.6 microM verapamil, and 0.1 microM flunarizine, whereas T-type ICa is halved by the same drugs at 0.6, 30, 30, and 0.1 microM, respectively. Diltiazem and verapamil accelerated the decay of L-type ICa and cumulatively blocked L-type ICa during repetitive step depolarizations elicited every 30 seconds ("use-dependent block"). Diltiazem and verapamil neither changed the decay of T-type ICa nor showed a use-dependent block of T-type ICa. Nicardipine and flunarizine blocked both L- and T-type ICa from the first depolarization step after drug treatment ("tonic block") and shifted their steady-state inactivation curves to the left. The estimated binding constants of nicardipine and flunarizine for the inactivated state of T-type Ca2+ channels (48 and 19 nM, respectively) were smaller than those for the resting state of L-type Ca2+ channels (160 and 90 nM, respectively). A low concentration (0.1 microM) of nicardipine initially potentiated T-type ICa and then reduced it. We conclude from these results that 1) nicardipine and flunarizine block not only the resting state but, more preferentially, the inactivated state of both the L- and T-type Ca2+ channels; 2) verapamil and diltiazem preferentially act on the open state of the L-type Ca2+ channel and on the resting and inactivated state of the T-type Ca2+ channel; and 3) the T-type Ca2+ channel of the rat aorta smooth muscle cells appears to be more sensitive to nicardipine and flunarizine than does the L-type Ca2+ channel at around the resting membrane potential.

Animals↗

PubMed1992

Cholesterol increases the L-type voltage-sensitive calcium channel current in arterial smooth muscle cells.

To determine whether membrane free cholesterol affects calcium currents in vascular smooth muscle cells, whole-cell patch clamp recordings were made before and after cholesterol enrichment of cells by exposure to cholesterol-rich liposomes. Exposure to cholesterol-rich liposomes resulted in a gradual increase in the L-type current over 20 hours and a plateau (73 +/- 7% increase over basal) between 20 and 32 hours. This effect was associated with a rightward shift in the inactivation potential and a decrease in the sensitivity to (-)-PN-202-791, a dihydropyridine antagonist. There was no change in the maximum L-type current stimulated by (+)-PN-202-791, a dihydropyridine agonist. Liposome exposure caused a small, transient increase in the T-type current (peak effect, 20 minutes). We conclude that membrane cholesterol has important effects on the L-type calcium current in vascular smooth muscle cells, which is most likely due to an alteration in channel functional state rather than an increase in channel expression.

Animals↗

PubMed1990

Dopamine inhibits two characterized voltage-dependent calcium currents in identified rat lactotroph cells.

The effects of dopamine (DA) on voltage-dependent Ca2+ currents were investigated in cultured rat lactotroph cells using the patch clamp recording technique. Each recorded cell was identified by the reverse hemolytic plaque assay. In the whole-cell configuration, two types of Ca2+ currents, L and T, were characterized on the basis of their kinetics, voltage sensitivity, and pharmacology. The L component had a threshold of -25 mV, showed little inactivation during a 150-msec voltage step, and was maximal at +10 mV. Cadmium ions (100 microM) significantly reduced its amplitude (75%). The T component was activated at a membrane potential close to -50 mV, was maximal at -10 mV, and showed a voltage-dependent inactivation between -90 and -30 mV. It was quickly inactivated during a maintained depolarization (time constant, 27 ms at -30 mV) and was strongly reduced (80%) by nickel ions (100 microM). Bath application of DA (10 nM) caused a markedly general depression of inward Ca2+ currents, acting differently on the T- and L-type currents. DA application shifted the voltage-dependence of the L-type current activation toward depolarization values (8 mV) without modifying its time- and voltage-dependent inactivation. In contrast, DA enhanced the inactivation of the T-type current by accelerating its time-dependent inactivation (25% decrease in the time constant of inactivation) and by shifting the voltage-dependence of the T-type current inactivation toward hyperpolarizing values (-63 mV in control vs. -77 mV in the presence of DA). These effects of DA were dose-dependent and involved the activation of a D2 receptor type. They were mimicked by bromocriptine application (10 nM), whereas sulpiride (100 nM) blocked the DA-evoked response. The D1 antagonist SCH 23390 was ineffective up to 100 microM. All of these DA-induced modifications in Ca2+ currents were abolished using a GTP-free pipette solution or after pretreatment of cells with pertussis toxin, suggesting that DA can regulate the function of Ca2+ channels through GTP-binding proteins (G-proteins). Our results show that DA acts simultaneously by reducing both voltage-dependent Ca2+ currents on lactotroph cells. Thus, DA reduces the entry of Ca2+ ions across the surface membrane and thereby influences electrical activity and the cytosolic free Ca2+ concentration involved in both basal and evoked PRL release.

Animals↗

PubMed1991

Reevaluation of the electrophysiological actions of thyrotropin-releasing hormone in a rat pituitary cell line (GH3).

The electrophysiological actions of TRH were examined in the clonal pituitary cell line GH3 with the use of the perforated patch variation of the standard whole cell patch-clamp technique. The action of TRH on spontaneously spiking cells was to cause a brief hyperpolarization (first phase action), followed by a period during which action potential behavior was significantly modified (second phase action). The modifications during second phase action included a reduction in the slope of the up-stroke, a reduced peak potential, an increase in duration, and a depolarizing shift of the after-hyperpolarization. The modification of voltage- and calcium-dependent conductances that underlie these changes were investigated in voltage clamp experiments. During first phase action TRH was found to increase calcium-dependent potassium current. During second phase action TRH was found to significantly reduce the L-type calcium current (35%), with no alteration in the T-type calcium current. The second phase action of TRH on calcium-dependent potassium conductance was complex. First, a decrease was observed. This was followed by an increase that did not become fully manifest until after TRH was washed from the cell. TRH caused no change in voltage-dependent potassium current. These results indicate that the second phase action of TRH on action potential behavior in GH3 cells is mediated by a reduction in L-type calcium current and alterations in the behavior of calcium-dependent potassium currents, but not through changes in voltage-dependent potassium currents.

Action Potentials↗

PubMed1992

Fast Na+ channels and slow Ca2+ current in smooth muscle from pregnant rat uterus.

Smooth muscle cells normally do not possess fast Na+ 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 pulses, 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]o, and was inhibited by TTX (K0.5 = 27 nM). The slow inward current decayed slowly, was dependent on [Ca]o, and was inhibited by nifedipine. These results suggest that the fast inward current is a fast Na+ channel current, and that the slow inward current is a Ca2+ slow channel current. A fast-inactivating 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 dihydropyridine-sensitive slow Ca2+ channels. The number of fast Na+ channels increased during gestation. 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 Na+ channels, and it is 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 extent. 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). Figure 11 summarizes the possible mechanisms by which uterine contractility can be modulated. In contrast to vascular smooth muscle, neither ISO nor adenosine, which produce elevation of cyclic AMP, affected ICa and INa. Therefore, no arrow can be drawn between cA-PK/cG-PK and the Ca2+ slow channel.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗

PubMed1992

Interaction between stannous chloride and calcium channel blockers in frog neuromuscular transmission.

We have investigated the interactions between stannous chloride (SnCl2) and calcium (Ca) channel blockers on endplate potentials (e.p.p.) and on miniature endplate potentials (m.e.p.p.) to determine which type of channel (among L-, N-, and T-type) participates in the SnCl2-induced increase in Ca entry into motor nerve terminals. The e.p.p. amplitude augmented by 30 microM SnCl2 was decreased by cumulative addition of 10 microM CdCl2 or 0.5 microM omega-conotoxin but not by 10 microM NiCl2 or 5 microM nicardipine. The SnCl2 (30 microM)-induced rise in m.e.p.p. frequency in high-potassium medium was reduced by 0.5 microM omega-conotoxin but not by 5 microM nicardipine. These results suggest that activation of the N-type Ca channel is involved in the SnCl2-induced increase in Ca entry into the nerve terminals.

Animals↗

PubMed1992

Fast Na+ channels and slow Ca2+ current in smooth muscle from pregnant rat uterus.

Smooth muscle cells normally do not possess fast Na+ channels, but inward current is carried through two types of Ca2+ channels: slow (L-type) Ca2+ channels and fast (T-type) Ca2+ channels. Whole-cell voltage clamp was done on single smooth muscle cells isolated from the longitudinal layer of 18-day pregnant rat uterus. Depolarizing pulses, applied from a holding potential of -90 mV, evoked two types of inward current, fast and slow. The fast inward current decayed within 30 ms, depended on [Na]o, and was inhibited by TTX (K0.5 = 27 nM). The slow inward current decayed slowly, was dependent on [Ca]o (or Ba2+), and was inhibited by nifedipine. These results suggest that the fast inward current is a fast Na+ channel current, and that the slow inward current is a Ca2+ slow channel current. A fast-inactivating Ca2+ channel current was not evident. We conclude that the ion channels which generate inward currents in pregnant rat uterine cells are TTX-sensitive fast Na+ channels and dihydropyridine-sensitive slow Ca2+ channels. The number of fast Na+ channels increased during gestation. The averaged current density increased from 0 on day 5, to 0.19 on day 9, 0.56 on day 14, 0.90 on day 18, and 0.86 pA/pF on day 21. This almost linear increase occurs because of an increase in the fraction of cells which possess fast Na+ channels. 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 we suggest that the fast Na+ current may be involved in spread of excitation. 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) (but not IBa) to a small extent. 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 cannot be explained by a stimulation of ICa(s).

Animals↗

PubMed1991

Activation of N-type calcium channels by stannous chloride at frog motor nerve terminals.

Stannous chloride (SnCl2) increases the calcium (Ca) entry into motor nerve terminals through the voltage-dependent Ca channels. The present study has been conducted to determine which type of channel (i.e., L-, N-, or T-type) participates in the Ca entry increased by SnCl2 (0.1 mM)-induced enhancement of the inward Ca current was more strongly inhibited by CdCl2 (50 microM) or omega-conotoxin (0.1 microM) than by NiCl2 (50 microM) or nifedipine (10 microM), respectively. From the results obtained, it is concluded that SnCl2 increases the Ca entry into the nerve terminal by activating the N-type Ca channels.

Animals↗