Deterministic model of Cav3.1 Ca2+ channel and a proposed sequence of its conformations

Abstract

A family of current-time curves of T-type Ca_v3.1 Ca²⁺ channels available in the literature is simulated by a kinetic model differing from that used for the interpretation of all salient features of Na⁺ and Shaker K⁺ channels by the insertion of a multiplying factor expressing the difference between the working potential ϕ and the reversal potential ϕ_r. This deterministic model is also used to simulate experimental curves taken from the literature for steady-state 'fast inactivation' and for a gradual passage from fast to 'slow inactivation'. A depolarizing pulse induces fast or slow inactivation depending on whether it lasts 100-500 ms or about 1 min, and is believed to cause a collapse of the central pore near the selectivity filter (SF). A number of features of fast and slow inactivation of Ca_v3.1 Ca²⁺ channels are qualitatively interpreted on the basis of a sequence of conformational states. Briefly, the conformation responsible for 'fast inactivation' is assumed to have the activation gate open and the inactivation gate (i.e., the SF) inactive. Immediately after a depolarizing pulse, this conformation is inactive and requires a sufficiently long rest time at a far negative holding potential to recover from inactivation. 'Slow inactivation' is ascribed to a different conformation with the activation gate closed and the SF inactive.

Keywords: Activation gate; Fast inactivation; Recovery from inactivation; Selectivity filter; Slow inactivation; T-type calcium channels.