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

We studied the gating kinetics, especially the kinetics of recovery from inactivation, of T-type Ca2+ channels (T-channels) in thalamic neurons. The recovery course is associated with no discernible Ca2+ current and is characterized by an initial delay, as well as a subsequent exponential phase. These findings are qualitatively similar to previous observations on neuronal Na+ channels and suggest that T-channels also must deactivate to recover from inactivation. In contrast to Na+ channels in which both the delay and the time constant of the exponential phase are shortened with increasing hyperpolarization, in T-channels the time constant of the exponential recovery phase remains unchanged between -100 and -200 mV, although the initial delay is still shortened e-fold per 43 mV hyperpolarization over the same voltage range. The deactivating kinetics of tail T-currents also show a similar voltage dependence between -90 and -170 mV. According to the hinged-lid model of fast inactivation, these findings suggest that the affinity difference 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 much slower binding and unbinding kinetics, and the unbinding rates probably remain unchanged once the inactivated T-channel has gone through the initial steps of deactivation and "closes" the pore (with the activation gate). T-channels thus might have a more rigid hinge and a more abrupt conformational change in the inactivation machinery associated with opening and closing of the pore.