Depolarization-induced slowing of Ca2+ channel deactivation in squid neurons.

Properties of squid giant fiber lobe (GFL) Ca2+ channel deactivation (closing) were studied using whole-cell voltage clamp. Tail currents displayed biexponential decay, and fast and slow components of these tails exhibited similar external Ca(2+)- and voltage-dependence. Both components also shared similar inactivation properties. Increasing duration pulses to strongly depolarizing potentials caused a substantial slowing of the rate of deactivation for the fast component, and also led to an apparent conversion of fast tail currents to slow without an increase in total tail amplitude. A five-state kinetic model that computed the closing of channels differentially populating two open states could simulate the kinetic characteristics of GFL Ca2+ pulse and tail currents over a wide voltage range. The kinetics of the proposed state transition was very similar to the time course of relief of omega-Agatoxin IVA Ca2+ channel block with long pulses. A similar model predicted that the relief of block could occur via faster toxin dissociation from the second open state. Thus, GFL Ca2+ channels possess a unique form of voltage-dependent gating modification, in which maintained prior depolarization leads to a significant delay to channel closure at negative potentials. At the nerve terminal, amplified Ca2+ signals generated by such a mechanism might alter synaptic responses to repetitive stimulation.