Calcium-Sensitive Inactivation in the Gating of Single Calcium Channels

Yue, David T.; Backx, Peter H.; Imredy, John P.

doi:10.1126/science.2176745

Cited by 189 publications

(135 citation statements)

References 28 publications

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“…12B (McCleskey, Fox, Feldman & Tsien, 1986). Some of these channels show only voltage-dependent inactivation, while others exhibit Ca2+-dependent inactivation (Byerly & Hagiwara, 1988;Yue, Backx & Imredy, 1990 (Hadley & Hume, 1987;Campbell, Giles, Hume & Shibata, 1988;Akaike, Tsuda & Oyama, 1988 high-Ca2+ , ATP-free solution, all the Ca2+ current is eliminated (Byerly & Moody, 1984). This last result also argues against the second possibility, that intracellular Ca2`might reduce but not completely block Ca2+ channel opening.…”

Section: Ca2' Sensitivity Of Caa2+ Channelsmentioning

confidence: 38%

Photo‐released intracellular Ca2+ rapidly blocks Ba2+ current in Lymnaea neurons.

Johnson

Byerly

1993

The Journal of Physiology

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SUMMARY1. The effect of intracellular Ca2+ on Ba2+ current flowing through voltagedependent Ca2+ channels was studied using the whole-cell patch-clamp technique on isolated neurons from the snail Lymnaea stagnalis. Intracellular Ca2+ was increased by flash photolysis of the caged Ca2+ compound DM-nitrophen and measured with the optical indicator fluo-3.2. After the highest intensity flashes, peak Ba2+ current was blocked by 42 % with a time constant of 5 ms. The onset of the block followed a similar time course whether channels were activated or closed. The Ba2+ current surviving after the flash had the same voltage dependence of activation and rate of inactivation as did the total Ba2+ current before the flash.3. Recovery of the Ba2+ current from block was nearly complete and occurred with a time constant of 16 s. Multiple episodes of photolysis-induced block could be studied in the same cell when 7-10 min were allowed between flashes. In some cells, recovery from block was accompanied by a transient enhancement of the current above the pre-block magnitude.

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Section: Ca2' Sensitivity Of Caa2+ Channelsmentioning

confidence: 38%

Photo‐released intracellular Ca2+ rapidly blocks Ba2+ current in Lymnaea neurons.

Johnson

Byerly

1993

The Journal of Physiology

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“…In particular, any hypothesis supposing that Ca2+ could influence Ca2+ channel gating while passing through the channel pore cannot be tested by the approach used in this study, as it 266 Ca2+-DEPENDENT INACTIVATION OF Ca2+ CHANNELS involves increasing bulk cytosolic [Ca2+],. However, it has been pointed out that such a hypothesis has some difficulty explaining the slow time course with which Ca21-dependent inactivation occurs at the single-channel level (Yue, Backx & Imredy, 1990). This work was supported by the National Institutes of Health and the Maryland Heart Association.…”

Section: Resultsmentioning

confidence: 99%

Ca2+ and voltage inactivate Ca2+ channels in guinea‐pig ventricular myocytes through independent mechanisms.

Hadley

Lederer

1991

The Journal of Physiology

133

104

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SUMMARY1. L-type Ca2+ currents and Ca2+ channel gating currents were studied in isolated guinea-pig ventricular heart cells using the whole-cell patch-clamp technique, in order to investigate the mechanism of Ca2+-dependent inactivation. The effect of altering the intracellular Ca2+ concentration ([Ca2+]i) on these currents was studied through photorelease of intracellular Ca2+ ions using the photolabile Ca2+ chelators DM-nitrophen and nitr-5.2. We found that step increases in [Ca2+]i produced by photorelease could either increase or decrease the L-type Ca2+ current. Specifically, Ca2+ photorelease from DM-nitrophen almost exclusively caused inactivation of the Ca2+ current. In contrast, Ca2+ photorelease from nitr-5 had a biphasic effect: a small, rapid inactivation of the Ca2+ current was followed by a slow potentiation. These two Ca2+-dependent processes seemed to differ in their Ca2+ dependence, as small Ca2+ photoreleases elicited potentiation without a preceding inactivation, whereas larger photoreleases elicited both inactivation and potentiation.3. The mechanism of the Ca2+-dependent inactivation of Ca2+ channels was explored by comparing the effects of voltage and photoreleased Ca2+ on the Ca2+ current and the Ca2+ channel gating current. Voltage was found to reduce both the Ca2+ current and the gating current proportionally. However, Ca2+ photorelease from intracellular DM-nitrophen inactivated the Ca2+ current without having any effect on the gating current.4

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“…In addition to in a variety of invertebrate systems (Brehm and Eckert, 1978;Tillotson, 1979;Ashcroft and Stanfield, 1981;Eckert and Chad, 1984;Gutnick et al, 1989;Johnson and Byerly, 1993), Ca2+-dependent inactivation has been described for L-type Ca 2+ channels of mammalian cardiac muscle and neurohypophysis (Kass and Sanguinetti, 1984;Bechem and Pott, 1985;Kalman et al, 1988;Yue, Backx, and Imredy, 1990). Negative feedback control of Ca 2+ entry may be a common mechanism for the regulation of intracellular Ca z+ levels.…”

Section: Discussionmentioning

confidence: 99%

Inactivation of N-type calcium current in chick sensory neurons: calcium and voltage dependence.

Cox

Dunlap

1994

The Journal of General Physiology

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We have studied the inactivation of high-voltage-activated (HVA), t0-conotoxin-sensitive, N-type Ca 2+ current in embryonic chick dorsal root ganglion (DRG) neurons. Voltage steps from -80 to 0 mV produced inward Ca ~+ currents that inactivated in a biphasic manner and were fit well with the sum of two exponentials (with time constants of ~ 100 ms and > 1 s). As reported previously, upon depolarization of the holding potential to -40 mV, N current amplitude was significantly reduced and the rapid phase of inactivation all but eliminated (Nowycky, M. C., A. P. Fox, and R. W. be explained by a model in which N channels inactivate by both fast and slow voltage-dependent processes. Alternatively, kinetic models of Ca-dependent inactivation suggest that the biphasic kinetics and holding-potential-dependence of N current inactivation could be due to a combination of Ca-dependent and slow voltage-dependent inactivation mechanisms. To distinguish between these possibilities we have performed several experiments to test for the presence of Cadependent inactivation. Three lines of evidence suggest that N channels inactivate in a Ca-dependent manner. (a) The total extent of inactivation increased 50%, and the ratio of rapid to slow inactivation increased ~ twofold when the concentration of the Ca 2 § buffer, EGTA, in the patch pipette was reduced from 10 to 0.1 mM. (b) With low intracellular EGTA concentrations (0.1 mM), the ratio of rapid to slow inactivation was additionally increased when the extracellular Ca 2 § concentration was raised from 0.5 to 5 mM. (c) Substituting Na § for Ca 2 § as the permeant ion eliminated the rapid phase of inactivation. Other results do not support the notion of current-dependent inactivation, however. Although high intraceUular EGTA (10

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Calcium-Sensitive Inactivation in the Gating of Single Calcium Channels

Cited by 189 publications

References 28 publications

Photo‐released intracellular Ca2+ rapidly blocks Ba2+ current in Lymnaea neurons.

Photo‐released intracellular Ca2+ rapidly blocks Ba2+ current in Lymnaea neurons.

Ca2+ and voltage inactivate Ca2+ channels in guinea‐pig ventricular myocytes through independent mechanisms.

Inactivation of N-type calcium current in chick sensory neurons: calcium and voltage dependence.

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