T-type Ca2+ channels encode prior neuronal activity as modulated recovery rates

Abstract

T-type Ca2+ channels give rise to low-threshold inward currents that are central determinants of neuronal excitability. The availability of T-type Ca2+ channels is strongly influenced by voltage-dependent inactivation and recovery from inactivation. Here, we show that native and cloned T-type Ca2+ channel subunits selectively encode specific aspects of prior membrane potential changes via a powerful modulation of the rates with which these channels recover from inactivation. Increasing the duration of subthreshold (-70 to -55 mV) conditioning depolarizations caused a pronounced slowing of subsequent recovery frominactivation of both cloned (Cav 3.1-3.3) and native T-type channels (thalamic neurones). The scaling of recovery rateswith increasing duration of conditioning depolarizations could be well described by a power law function. Different T-type channel isoforms exhibited overlapping but complementary ranges of recovery rates. Intriguingly, scaling of recovery rates was dramatically reduced in Cav3.2 and Cav3.3, but not Cav3.1 subunits, when mock action potentials were superimposed on conditioning depolarizations. Our results suggest that different T-type channel subunits exhibit dramatic differences in scaling relationships, in addition to well-described differences in other biophysical properties. Furthermore, the availability of T-type channels is powerfully modulated over time, dependingonthe patterns of prior activity that these channels have encountered. These data provide a novel mechanism for cellular short-term plasticity on the millisecond to second time scale that relies on biophysical properties of specific T-type Ca2+ channel subunits. © 2006 The Authors. Journal compilation © 2006 The Physiological Society.