Analysis of the modal hypothesis of Ca2+-dependent inactivation of L-type Ca2+ channels.
A kinetic model of Ca2+-dependent inactivation (CDI) of L-type Ca2+ channels was developed. The model is based on the hypothesis that postulates the existence of four short-lived modes with lifetimes of a few hundreds of milliseconds. Our findings suggest that the transitions between the modes is primarily determined by the binding of Ca2+ to two intracellular allosteric sites located in different motifs of the CI region, which have greatly differing binding rates for Ca2+ (different k(on)). The slow-binding site is controlled by local Ca2+ near a single open channel that is consistent with the "domain" CDI model, and Ca2+ binding to the fast-binding site(s) depends on Ca2+ arising from distant sources that is consistent with the "shell" CDI model. The model helps to explain numerous experimental findings that are poorly understood so far.
Markevich
Nick I
NI
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow 142290, Russia. Nikolai.Markevitch@jefferson.edu
Pimenov
Oleg Y
OY
Kokoz
Yury M
YM
D002118:Calcium / Q000737:chemistry / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D013997:Time Factors
D020746:Calcium Channels, L-Type; D002118:Calcium