Divalent cation dependent inactivation of the high-voltage-activated Ca-channel current in chick sensory neurons

1988 ◽  
Vol 411 (6) ◽  
pp. 695-697 ◽  
Author(s):  
H. Kasai ◽  
T. Aosaki
Keyword(s):  
Sensory Neurons ◽  
High Voltage ◽  
Divalent Cation ◽  
Ca Channel ◽  
Channel Current ◽  
Dependent Inactivation ◽  
Ca Channel Current

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 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.

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.

Calcium Channel Activation Facilitated by Nitric Oxide in Retinal Ganglion Cells

2000 ◽  
Vol 83 (1) ◽  
pp. 198-206 ◽  
Author(s):  
Kazuyuki Hirooka ◽  
Dmitri E. Kourennyi ◽  
Steven Barnes
Keyword(s):  
Protein Kinase ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Peptide Inhibitor ◽  
Ca Channel ◽  
Retinal Ganglion ◽  
Ca Channels ◽  
Channel Current ◽  
Channel Currents ◽  
Ca Channel Current

We investigated the modulation of voltage-gated Ca channels by nitric oxide (NO) in isolated salamander retinal ganglion cells with the goals of determining the type of Ca channel affected and the signaling pathway by which modulation might occur. The NO donors, S-nitroso- N-acetyl-penicillamine (SNAP, 1 mM) and S-nitroso-cysteine (1 mM) induced modest increases in the amplitude of Ca channel currents recorded with ruptured- and permeabilized-patch techniques by causing a subpopulation of the Ca channels to activate at more negative potentials. The Ca channel antagonists ω-conotoxin GVIA and nisoldipine each reduced the Ca channel current partially, but only ω-conotoxin GVIA blocked the enhancement by SNAP. The SNAP-induced increase was blocked by oxadiazolo-quinoxaline (50 μM), suggesting that the NO generated by SNAP acts via a soluble guanylyl cyclase to raise levels of cGMP. The membrane-permeant cGMP analog 8-(4-chlorophenylthio) guanosine cyclic monophosphate also enhanced Ca channel currents and 8-bromo guanosine cyclic monophosphate (1 mM) occluded enhancement by SNAP. Consistent with these results, isobutyl-methyl-xanthine (IBMX, 10 μM), which can raise cGMP levels by inhibiting phosphodiesterase activity, increased Ca channel current by the same amount as SNAP and occluded subsequent enhancement by SNAP. Neither IBMX, the cGMP analogs, nor SNAP itself, led to activation of cGMP-gated channels. N-[2-(methylamino)ethyl]−5-isoquinoline-sulfonamide (2 μM), a broad spectrum inhibitor of protein kinase activity, KT5823 (1 μM), a specific protein kinase G (PKG) inhibitor, and a peptide inhibitor of PKG (200 μM) blocked SNAP enhancement, as did 5′-adenylylimidophosphate (1.5 mM), a nonhydrolyzable ATP analog that prevents protein phosphorylation. A peptide inhibitor of protein kinase A (10 nM) did not block the facilitory effects of SNAP. Okadaic acid (1 μM), a phosphatase inhibitor, had no effect by itself but increased the enhancement of Ca channel current by SNAP. These results suggest that NO modulates retinal ganglion cell N-type Ca channels by facilitating their voltage-dependent activation via a mechanism involving guanylyl cyclase/PKG-dependent phosphorylation. This effect could fine-tune neural integration in ganglion cells or play a role in ganglion cell disease by modulating intracellular calcium signaling.

L-type calcium channel α-subunit and protein kinase inhibitors modulate Rem-mediated regulation of current

2006 ◽  
Vol 291 (4) ◽  
pp. H1959-H1971 ◽  
Author(s):  
Shawn M. Crump ◽  
Robert N. Correll ◽  
Elizabeth A. Schroder ◽  
William C. Lester ◽  
Brian S. Finlin ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitors ◽  
Small Gtpases ◽  
Protein Kinase Inhibitors ◽  
Ca Channel ◽  
Α Subunit ◽  
Hek 293 ◽  
Channel Current ◽  
Channel Inhibition ◽  
Ca Channel Current

Cardiac voltage-gated L-type Ca channels (CaV) are multiprotein complexes, including accessory subunits such as CaVβ2 that increase current expression. Recently, members of the Rad and Gem/Kir-related family of small GTPases have been shown to decrease current, although the mechanism remains poorly defined. In this study, we evaluated the contribution of the L-type Ca channel α-subunit (CaV1.2) to CaVβ2-Rem inhibition of Ca channel current. Specifically, we addressed whether protein kinase A (PKA) modulation of the Ca channel modifies CaVβ2-Rem inhibition of Ca channel current. We first tested the effect of Rem on CaV1.2 in human embryonic kidney 293 (HEK-293) cells using the whole cell patch-clamp configuration. Rem coexpression with CaV1.2 reduces Ba current expression under basal conditions, and CaVβ2a coexpression enhances Rem block of CaV1.2 current. Surprisingly, PKA inhibition by 133 nM H-89 or 50 μM Rp-cAMP-S partially relieved the Rem-mediated inhibition of current activity both with and without CaVβ2a. To test whether the H-89 action was a consequence of the phosphorylation status of CaV1.2, we examined Rem regulation of the PKA-insensitive CaV1.2 serine 1928 (S1928) to alanine mutation (CaV1.2-S1928A). CaV1.2-S1928A current was not inhibited by Rem and when coexpression with CaVβ2a was not completely blocked by Rem coexpression, suggesting that the phosphorylation of S1928 contributes to Rem-mediated Ca channel modulation. As a model for native Ca channel complexes, we tested the ability of Rem overexpression in HIT-T15 cells and embryonic ventricular myocytes to interfere with native current. We find that native current is also sensitive to Rem block and that H-89 pretreatment relieves the ability of Rem to regulate Ca current. We conclude that Rem is capable of regulating L-type current, that release of Rem block is modulated by cellular kinase pathways, and that the CaV1.2 COOH terminus contributes to Rem-dependent channel inhibition.

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