MOLECULAR CHARACTERIZATION OF A NEURONAL LOW-VOLTAGE-ACTIVATED T-TYPECALCIUM-CHANNEL

The molecular diversity of voltage-activated calcium channels was esta blished by studies showing that channels could be distinguished by the ir voltage-dependence, deactivation and single-channel conductance(1-3 ). Low-voltage-activated channels are called 'T' type because their cu rrents are both transient (owing. to fast inactivation) and tiny (owin g to small conductance)(2). T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscilla tions and resonance, and rebound burst firing(4). Here we report the i dentification of a neuronal T-type channel. Our cloning strategy began with an analysis of Genbank sequences defined as sharing homology wit h calcium channels. We sequenced an expressed sequence tag (EST), then used it to done a full-length complementary DNA from rat brain. North ern blot analysis indicated that this gene is expressed predominantly in brain, in particular the amygdala, cerebellum and thalamus. We mapp ed the human gene to chromosome 17q22, and the mouse gene to chromosom e 11. Functional expression of the channel was measured in Xenopus ooc ytes. Based on the channel's distinctive voltage dependence, slow deac tivation kinetics, and 7.5-pS single-channel conductance, we conclude that this channel is a low-voltage-activated T-type calcium channel.