InterPro domain: IPR043203

T-type calcium channels exhibit unique voltage-dependent kinetics, small single channel conductance, rapid inactivation, slow deactivation and a relatively high permeability to calcium [ 1 ]. They are primarily responsible for rebound burst firing in central neurons and are implicated in normal brain functions, such as slow wave sleep, and in diseased states, such as epilepsy [ 2 ]. They also play an important role in hormone secretion [ 2 ] and smooth muscle excitability [ 3 ].

This entry represents alpha subunits of the voltage-gated sodium channel superfamily and the alpha-1 subunit of T-type calcium channels.

Voltage-dependent sodium channels are transmembrane (TM) proteins are responsible for the depolarising phase of the action potential in most electrically excitable cells [ 4 ]. Several structural and functional isoforms are found in mammals, coded for by a multigene family, which leads to different types of sodium ion in excitable tissues.

Voltage-dependent calcium channels (VDCC) are a family of molecules that allow cells to couple electrical activity to intracellular calcium signalling. The opening and closing of these channels by depolarizing stimuli allows calcium ions to enter neurons down a steep electrochemical gradient, producing transient intracellular calcium signals. The pore is formed by the alpha-1 subunit which incorporates the conduction pore, the voltage sensor and gating apparatus and the known sites of channel regulation by second messengers, drugs, and toxins [ 5 ].

The structure of sodium channels is based on 4 internal repeats of a 6-helix bundle [ 6 ]. The basic structural motif (the 6-helix bundle) is also found in potassium and calcium channel alpha subunits.

1. Low-threshold calcium currents in central nervous system neurons. Annu. Rev. Physiol. 58, 329-48
2. T-type Ca2+ channels are required for adrenocorticotropin-stimulated cortisol production by bovine adrenal zona fasciculata cells. Mol. Endocrinol. 7, 1031-40
3. Dihydropyridine-sensitive low-threshold calcium channels in isolated rat hypothalamic neurones. J. Physiol. (Lond.) 412, 181-95
4. Molecular cloning of an atypical voltage-gated sodium channel expressed in human heart and uterus: evidence for a distinct gene family. Proc. Natl. Acad. Sci. U.S.A. 89, 4893-7
5. International Union of Pharmacology. XL. Compendium of voltage-gated ion channels: calcium channels. Pharmacol. Rev. 55, 579-81
6. Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence. Nature 312, 121-7