Molecular and functional characterization of a family of rat brain T-type calcium channels

Voltage-gated calcium channels represent a heterogenous family of calcium-s elective channels that can be distinguished by their molecular, electrophys iological, and pharmacological characteristics. We report here the molecula r cloning and functional expression of three members of the low voltage-act ivated calcium channel family from rat brain (alpha (1G), alpha (1H) and al pha (1I)). Northern blot and reverse transcriptase-polymerase chain reactio n analyses show alpha (1G), and alpha (1H), and alpha (1I) to be expressed throughout the newborn and juvenile rat brain. In contrast, while alpha (1G ) and alpha (1H) mRNA are expressed in all regions in adult rat brain, alph a (1I) mRNA expression is restricted to the striatum. Expression of alpha ( 1G), alpha (1H), and alpha (1I) subunits in HEK293 cells resulted in calciu m currents with typical T-type channel characteristics: low voltage activat ion, negative steady-state inactivation, strongly voltage-dependent activat ion and inactivation, and slow deactivation, In addition, the direct electr ophysiological comparison of alpha (1G), alpha (1H), and alpha (1I) under i dentical recording conditions also identified unique characteristics includ ing activation and inactivation kinetics and permeability to divalent catio ns. Simulation of alpha (IG),alpha (1H), and alpha (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 channe l types make distinct contributions to neuronal physiology.