Molecular and Functional Characterization of a Family of Rat Brain T-type Calcium Channels

Abstract

Voltage-gated calcium channels represent a heterogenous family of calcium-selective channels that can be distinguished by their molecular, electrophysiological, and pharmacological characteristics. We report here the molecular cloning and functional expression of three members of the low voltage-activated calcium channel family from rat brain (α1G, α1H, and α1I). Northern blot and reverse transcriptase-polymerase chain reaction analyses show α1G, α1H, and α1I to be expressed throughout the newborn and juvenile rat brain. In contrast, while α1G and α1H mRNA are expressed in all regions in adult rat brain, α1I mRNA expression is restricted to the striatum. Expression of α1G, α1H, and α1I subunits in HEK293 cells resulted in calcium currents with typical T-type channel characteristics: low voltage activation, negative steady-state inactivation, strongly voltage-dependent activation and inactivation, and slow deactivation. In addition, the direct electrophysiological comparison of α1G, α1H, and α1I under identical recording conditions also identified unique characteristics including activation and inactivation kinetics and permeability to divalent cations. Simulation of α1G, α1H, and α 1I T-type channels in a thalamic neuron model cell produced unique firing patterns (burst versus tonic) typical of different brain nuclei and suggests that the three channel types make distinct contributions to neuronal physiology.