Physiology and Pathology of Voltage-Gated T-Type Calcium Channels

T-type channels are low voltage-activated members of the calcium channel family that also includes the high voltage-activated Cav1 and Cav2 channels. T-type channels open with only minimal depolarization or in response to hyperpolarization of the cell membrane and are associated with regulating excitability and pacemaking at subthreshold voltages. Interestingly, increasing evidence suggests that the subthreshold properties of T-type channels are exploited for other cellular processes including low-threshold synaptic vesicle release (excitation-secretion coupling), myocyte contraction and tone (excitation-contraction coupling), and cell cycle control. T-type channels are implicated in several pathologies including epilepsy, autism, sleep disturbances, pain, hypertension, and cancer. With the advent of novel blockers selective for T-type channels, their important contributions to normal cellular/organismal physiology, as well as to pathology, are becoming clearer.