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

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 (α_1G, α_1H, and α_1I). Northern blot and reverse transcriptase-polymerase chain reaction analyses show α_1G, α_1H, and α_1I to be expressed throughout the newborn and juvenile rat brain. In contrast, while α_1G and α_1H mRNA are expressed in all regions in adult rat brain, α_1I mRNA expression is restricted to the striatum. Expression of α_1G, α_1H, and α_1I 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 α_1G, α_1H, and α_1I under identical recording conditions also identified unique characteristics including activation and inactivation kinetics and permeability to divalent cations. Simulation of α_1G, α_1H, 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.