Recovery from inactivation of T-type Ca2+ channels in rat thalamic neurons

We studied the gating kinetics, especially the kinetics of recovery from in activation, of T-type Ca2+ channels (T-channels) in thalamic neurons. The r ecovery course is associated with no discernible Ca2+ current and is charac terized by an initial delay, as well as a subsequent exponential phase. The se findings are qualitatively similar to previous observations on neuronal Na+ channels and suggest that T-channels also must deactivate to recover fr om inactivation. In contrast to Na+ channels in which both the delay and th e time constant of the exponential phase are shortened with increasing hype rpolarization, in T-channels the time constant of the exponential recovery phase remains unchanged between -100 and -200 mV, although the initial dela y is still shortened e-fold per 43 mV hyperpolarization over the same volta ge range. The deactivating kinetics of tail T-currents also show a similar voltage dependence between -90 and -170 mV. According to the hinged-lid mod el of fast inactivation, these findings suggest that the affinity differenc e between inactivating peptide binding to the activated channel and binding to the fully deactivated channel is much smaller in T-channels than in Na channels. Moreover, the inactivating peptide in T-channels seems to have m uch slower binding and unbinding kinetics, and the unbinding rates probably remain unchanged once the inactivated T-channel has gone through the initi al steps of deactivation and "closes" the pore (with the activation gate). T-channels thus might have a more rigid hinge and a more abrupt conformatio nal change in the inactivation machinery associated with opening and closin g of the pore.