Mechanism of Ca$^2+$-sensitive inactivation of L-type Ca$^2+$
channels.
J. Imredy, and D. Yue. Neuron, 12 (6):
1301--1318(June 1994)
Abstract
Many high threshold, voltage-gated Ca$^2+$ channels, including
the dihydropyridine-sensitive class (L-type), inactivate in response
not only to voltage, but also to entry of Ca$^2+$. Despite the
physiological importance of this Ca$^2+$-sensitive inactivation,
its molecular mechanism is understood only in broad outline. We now
demonstrate that Ca$^2+$-dependent inactivation transpires by
a Ca$^2+$-induced shift of channel gating to a low open probability
mode, distinguished by a more than 100-fold reduction of entry rate
to the open state. A gating mechanism that explains this shift quantitatively
and enables successful separation of Ca$^2+$- and voltage-sensitive
forms of inactivation is deduced and tested. Finally, both calmodulin
activation and channel (de)phosphorylation are excluded as significant
signaling events underlying Ca$^2+$-induced mode shifts, leaving
direct binding of Ca$^2+$ to the channel as a likely chemical
initiation event for inactivation.
%0 Journal Article
%1 Imre_1994_1301
%A Imredy, J. P.
%A Yue, D. T.
%D 1994
%J Neuron
%K 8011340 Animals, Barium, Biological, Calcium Calcium, Cells, Channel Channels, Cultured, Dihydropyridines, Factors, Gating, Gov't, Heart, Ion Mathematics, Membrane Models, Non-U.S. P.H.S., Potentials, Probability, Rats, Research Signal Support, Time Transduction, U.S.
%N 6
%P 1301--1318
%T Mechanism of Ca$^2+$-sensitive inactivation of L-type Ca$^2+$
channels.
%V 12
%X Many high threshold, voltage-gated Ca$^2+$ channels, including
the dihydropyridine-sensitive class (L-type), inactivate in response
not only to voltage, but also to entry of Ca$^2+$. Despite the
physiological importance of this Ca$^2+$-sensitive inactivation,
its molecular mechanism is understood only in broad outline. We now
demonstrate that Ca$^2+$-dependent inactivation transpires by
a Ca$^2+$-induced shift of channel gating to a low open probability
mode, distinguished by a more than 100-fold reduction of entry rate
to the open state. A gating mechanism that explains this shift quantitatively
and enables successful separation of Ca$^2+$- and voltage-sensitive
forms of inactivation is deduced and tested. Finally, both calmodulin
activation and channel (de)phosphorylation are excluded as significant
signaling events underlying Ca$^2+$-induced mode shifts, leaving
direct binding of Ca$^2+$ to the channel as a likely chemical
initiation event for inactivation.
@article{Imre_1994_1301,
abstract = {Many high threshold, voltage-gated {C}a$^{2+}$ channels, including
the dihydropyridine-sensitive class (L-type), inactivate in response
not only to voltage, but also to entry of {C}a$^{2+}$. Despite the
physiological importance of this {C}a$^{2+}$-sensitive inactivation,
its molecular mechanism is understood only in broad outline. We now
demonstrate that {C}a$^{2+}$-dependent inactivation transpires by
a {C}a$^{2+}$-induced shift of channel gating to a low open probability
mode, distinguished by a more than 100-fold reduction of entry rate
to the open state. A gating mechanism that explains this shift quantitatively
and enables successful separation of {C}a$^{2+}$- and voltage-sensitive
forms of inactivation is deduced and tested. Finally, both calmodulin
activation and channel (de)phosphorylation are excluded as significant
signaling events underlying {C}a$^{2+}$-induced mode shifts, leaving
direct binding of {C}a$^{2+}$ to the channel as a likely chemical
initiation event for inactivation.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Imredy, J. P. and Yue, D. T.},
biburl = {https://www.bibsonomy.org/bibtex/267d6a3126396562d95963e791a964a06/hake},
description = {The whole bibliography file I use.},
interhash = {77ea570b16cd63891a40a47727ad6e9b},
intrahash = {67d6a3126396562d95963e791a964a06},
journal = {Neuron},
key = 100,
keywords = {8011340 Animals, Barium, Biological, Calcium Calcium, Cells, Channel Channels, Cultured, Dihydropyridines, Factors, Gating, Gov't, Heart, Ion Mathematics, Membrane Models, Non-U.S. P.H.S., Potentials, Probability, Rats, Research Signal Support, Time Transduction, U.S.},
month = Jun,
number = 6,
pages = {1301--1318},
pmid = {8011340},
timestamp = {2009-06-03T11:21:16.000+0200},
title = {Mechanism of {C}a$^{2+}$-sensitive inactivation of L-type {C}a$^{2+}$
channels.},
volume = 12,
year = 1994
}