%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 }