scholarly journals Inactivation of calcium channel current in the calf cardiac Purkinje fiber. Evidence for voltage- and calcium-mediated mechanisms.

1984 ◽  
Vol 84 (5) ◽  
pp. 705-726 ◽  
Author(s):  
R S Kass ◽  
M C Sanguinetti
Keyword(s):  
Charge Carrier ◽  
Divalent Cations ◽  
Purkinje Fiber ◽  
Ca Channel ◽  
Channel Current ◽  
Zero Current ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Ca Channel Current ◽  
Dependent Mechanism

We have studied the influence of divalent cations on Ca channel current in the calf cardiac Purkinje fiber to determine whether this current inactivates by voltage- or Ca-mediated mechanisms, or by a combination of the two. We measured the reversal (or zero current) potential of the current when Ba, Sr, or Ca were the permeant divalent cations and determined that depletion of charge carrier does not account for time-dependent relaxation of Ca channel current in these preparations. Inactivation of Ca channel current persists when Ba or Sr replaces Ca as the permeant divalent cation, but the voltage dependence of the rate of inactivation is markedly changed. This effect cannot be explained by changes in external surface charge. Instead, we interpret the results as evidence that inactivation is both voltage and Ca dependent. Inactivation of Sr or Ba currents reflects a voltage-dependent process. When Ca is the divalent charge carrier, an additional effect is observed: the rate of inactivation is increased as Ca enters during depolarizing pulses, perhaps because of an additional Ca-dependent mechanism.

scholarly journals Modulation of voltage-dependent Ca channel current by arachidonic acid and other long-chain fatty acids in rabbit intestinal smooth muscle.

1992 ◽  
Vol 100 (1) ◽  
pp. 27-44 ◽  
Author(s):  
T Shimada ◽  
A P Somlyo
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Ca Channel ◽  
Long Chain Fatty Acids ◽  
Channel Current ◽  
Kinase C ◽  
Voltage Dependent ◽  
Ca Channel Current ◽  
Long Chain

The effects of arachidonic acid (AA) and other long-chain fatty acids on voltage-dependent Ca channel current (ICa) were investigated, with the whole cell patch clamp method, in longitudinal smooth muscle cells of rabbit ileum. 10-30 microM AA caused a gradual depression of ICa. The inhibitory effect of AA was not prevented by indomethacin (10 microM) (an inhibitor of cyclooxygenase) or nordihydroguaiaretic acid (10 microM) (an inhibitor of lipoxygenase). 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine (H7; 25-50 microM) or staurosporine (2 microM) (inhibitors of protein kinase C) did not block the AA-induced inhibition of ICa, and application of phorbol ester (a protein kinase C activator) (phorbol-12,13-dibutyrate, 0.2 microM) did not mimic the AA action. Some other cis-unsaturated fatty acids (palmitoleic, linoleic, and oleic acids) were also found to depress ICa, while a trans-unsaturated fatty acid (linolelaidic acid) and saturated fatty acids (capric, lauric, myristic, and palmitic acids) had no inhibitory effects on ICa. Myristic acid consistently increased the amplitude of ICa at negative membrane potentials. The present results suggest the possible role of AA, and perhaps other fatty acids, in the physiological and/or pathological modulation of ICa in smooth muscle.

scholarly journals The dihydropyridine-sensitive calcium channel subtype in cone photoreceptors.

1996 ◽  
Vol 107 (5) ◽  
pp. 621-630 ◽  
Author(s):  
M F Wilkinson ◽  
S Barnes
Keyword(s):  
Channel Blocker ◽  
Channel Blockers ◽  
Ca Channel ◽  
Ca Channels ◽  
Cone Photoreceptors ◽  
Channel Current ◽  
Ca Channel Blockers ◽  
Voltage Dependent ◽  
P Type ◽  
Ca Channel Current

High-voltage activated Ca channels in tiger salamander cone photoreceptors were studied with nystatin-permeabilized patch recordings in 3 mM Ca2+ and 10 mM Ba2+. The majority of Ca channel current was dihydropyridine sensitive, suggesting a preponderance of L-type Ca channels. However, voltage-dependent, incomplete block (maximum 60%) by nifedipine (0.1-100 microM) was evident in recordings of cones in tissue slice. In isolated cones, where the block was more potent, nifedipine (0.1-10 microM) or nisoldipine (0.5-5 microM) still failed to eliminate completely the Ca channel current. Nisoldipine was equally effective in blocking Ca channel current elicited in the presence of 10 mM Ba2+ (76% block) or 3 mM Ca2+ (88% block). 15% of the Ba2+ current was reversibly blocked by omega-conotoxin GVIA (1 microM). After enhancement with 1 microM Bay K 8644, omega-conotoxin GVIA blocked a greater proportion (22%) of Ba2+ current than in control. After achieving partial block of the Ba2+ current with nifedipine, concomitant application of omega-conotoxin GVIA produced no further block. The P-type Ca channel blocker, omega-agatoxin IVA (200 nM), had variable and insignificant effects. The current persisting in the presence of these blockers could be eliminated with Cd2+ (100 microM). These results indicate that photoreceptors express an L-type Ca channel having a distinguishing pharmacological profile similar to the alpha 1D Ca channel subtype. The presence of additional Ca channel subtypes, resistant to the widely used L-, N-, and P-type Ca channel blockers, cannot, however, be ruled out.

scholarly journals Permeation and interaction of divalent cations in calcium channels of snail neurons.

1985 ◽  
Vol 85 (4) ◽  
pp. 491-518 ◽  
Author(s):  
L Byerly ◽  
P B Chase ◽  
J R Stimers
Keyword(s):  
Mole Fraction ◽  
Surface Potential ◽  
Divalent Cation ◽  
Lymnaea Stagnalis ◽  
Divalent Cations ◽  
Ca Channel ◽  
Ca Current ◽  
Channel Current ◽  
Gating Mechanism ◽  
Ca Channel Current

We have studied the current-carrying ability and blocking action of various divalent cations in the Ca channel of Lymnaea stagnalis neurons. Changing the concentration or species of the permeant divalent cation shifts the voltage dependence of activation of the Ca channel current in a manner that is consistent with the action of the divalent cation on an external surface potential. Increasing the concentration of the permeant cation from 1 to 30 mM produces a twofold increase in the maximum Ca current and a fourfold increase in the maximum Ba current; the maximum Ba current is twice the size of the maximum Ca current for 10 mM bulk concentration. Correcting for the changing surface potential seen by the gating mechanism, the current-concentration relation is almost linear for Ba2+, and shows only moderate saturation for Ca2+; also, Ca2+, Ba2+, and Sr2+ are found to pass through the channel almost equally well. These conclusions are obtained for either of two assumptions: that the mouth of the channel sees (a) all or (b) none of the surface potential seen by the gating mechanism. Cd2+ blocks Lymnaea and Helix Ca channels at concentrations 200 times smaller than those required for Co2+ or Ni2+. Ca2+ competes with Cd2+ for the blocking site; Ba2+ binds less strongly than Ca2+ to this site. Mixtures of Ca2+ and Ba2+ produce an anomalous mole fraction effect on the Ca channel current. After correction for the changing surface potential (using either assumption), the anomalous mole fraction effect is even more prominent, which suggests that Ba2+ blocks Ca current more than Ca2+ blocks Ba current.

Determination of Pure Voltage-Dependent Ca2+ Current in Paramecium Caudatum and its Inhibition by Divalent Cations

1985 ◽  
Vol 119 (1) ◽  
pp. 321-334
Author(s):  
FRANK WEHNER ◽  
EILO HILDEBRAND
Keyword(s):  
Dissociation Constants ◽  
Divalent Cations ◽  
Equilibrium Potential ◽  
Ca Channel ◽  
Paramecium Caudatum ◽  
Voltage Range ◽  
Outward Currents ◽  
Voltage Dependent ◽  
Inward Currents

Voltage-dependent Ca2+ currents in Paramecium caudatum were studied under voltage clamp conditions. To separate Ca2+ inward currents from concomitant K+ outward currents, the voltage-dependent Ca2+ conductance was temporarily inactivated by a preceding depolarization. The remaining currents were then subtracted from the overall currents measured in the absence of a prepulse. In this way pure Ca2+ currents could be obtained up to a depolarization of 100 mV, which is about 50 mV below the theoretical Ca2+ equilibrium potential (Eca). Ca2+ currents were maximal at a depolarization of 35 mV and declined with further approach to Eca, but they did not reverse sign in the voltage range tested. In the presence of Mg2+, Co2+, Mn2+ or Ni2+, the Ca2+ inward currents decreased to a different extent. From experiments where these cations were added at different concentrations and from measurements at different Ca2+ concentrations in the absence of other divalent cations the following ratio of apparent dissociation constants could be derived: kNi: kco: kca: kMg = 1:3:4.3-4.7:5:6.5. With a confidence of 95% the absolute value of kca lies between 40 and 130μmol l−1. These results indicate that Ca2+ and other divalent cations compete for binding sites at the Ca-channel and thus determine excitability. Indirect effects due to changes of the surface potential are discussed.

scholarly journals Mechanism of Cgmp-Gated Channel Block by Intracellular Polyamines

2000 ◽  
Vol 115 (6) ◽  
pp. 783-798 ◽  
Author(s):  
Donglin Guo ◽  
Zhe Lu
Keyword(s):  
Minimal Model ◽  
Membrane Voltage ◽  
Channel Block ◽  
Channel Current ◽  
Channel Blocking ◽  
Voltage Dependent ◽  
Gated Channel ◽  
Blocking Mechanism ◽  
Complex Channel ◽  
Dependent Mechanism

Polyamines block the retinal cyclic nucleotide-gated channel from both the intracellular and extracellular sides. The voltage-dependent mechanism by which intracellular polyamines inhibit the channel current is complex: as membrane voltage is increased in the presence of polyamines, current inhibition is not monotonic, but exhibits a pronounced damped undulation. To understand the blocking mechanism of intracellular polyamines, we systematically studied the endogenous polyamines as well as a series of derivatives. The complex channel-blocking behavior of polyamines can be accounted for by a minimal model whereby a given polyamine species (e.g., spermine) causes multiple blocked channel states. Each blocked state represents a channel occupied by a polyamine molecule with characteristic affinity and probability of traversing the pore, and exhibits a characteristic dependence on membrane voltage and cGMP concentration.

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