DEPOLARIZATION-INDUCED SLOWING OF CA2+ CHANNEL DEACTIVATION IN SQUID NEURONS

Properties of squid giant fiber robe (GFL) Ca2+ channel deactivation ( closing) were studied using whole-cell voltage clamp, Tail currents di splayed biexponential decay, and fast and slow components of these tai ls exhibited similar external Ca2+- and voltage-dependence. Both compo nents also shared similar inactivation properties, Increasing duration pulses to strongly depolarizing potentials caused a substantial slowi ng of the rate of deactivation for the fast component, and also led to an apparent conversion of fast tail currents to slow without an incre ase in total tail amplitude, A five-state kinetic model that computed the closing of channels differentially populating two open slates coul d simulate the kinetic characteristics of GFL Ca2+ pulse and tail curr ents over a wide voltage range, The kinetics of the proposed state tra nsition was very similar to the time course of relief of omega-Agatoxi n IVA Ca2+ channel block with long pulses. A similar model predicted t hat 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 de polarization leads to a significant delay to channel closure at negati ve potentials, At the nerve terminal, amplified Ca2+ signals generated by such a mechanism might alter synaptic responses to repetitive stim ulation.