Voltage-dependent calcium channel, T-type, alpha-1 subunit (IPR005445)
Short name: VDCC_T_a1
Overlapping homologous superfamilies
- Voltage-dependent calcium channel, alpha-1 subunit (IPR002077)
- Voltage-dependent calcium channel, T-type, alpha-1 subunit (IPR005445)
Ca2+ ions are unique in that they not only carry charge but they are also the most widely used of diffusible second messengers. Voltage-dependent Ca2+ channels (VDCC) are a family of molecules that allow cells to couple electrical activity to intracellular Ca2+ signalling. The opening and closing of these channels by depolarizing stimuli, such as action potentials, allows Ca2+ ions to enter neurons down a steep electrochemical gradient, producing transient intracellular Ca2+ signals. Many of the processes that occur in neurons, including transmitter release, gene transcription and metabolism are controlled by Ca2+ influx occurring simultaneously at different cellular locales. 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 [PMID: 14657414]. The activity of this pore is modulated by four tightly-coupled subunits: an intracellular beta subunit; a transmembrane gamma subunit; and a disulphide-linked complex of alpha-2 and delta subunits, which are proteolytically cleaved from the same gene product. Properties of the protein including gating voltage-dependence, G protein modulation and kinase susceptibility can be influenced by these subunits.
Voltage-gated calcium channels are classified as T, L, N, P, Q and R, and are distinguished by their sensitivity to pharmacological blocks, single-channel conductance kinetics, and voltage-dependence. On the basis of their voltage activation properties, the voltage-gated calcium classes can be further divided into two broad groups: the low (T-type) and high (L, N, P, Q and R-type) threshold-activated channels.
The alpha-1 subunit forms the pore for the import of extracellular calcium ions and, though regulated by the other subunits, is primarily responsible for the pharmacological properties of the channel [PMID: 11031246]. It shares sequence characteristics with all voltage-dependent cation channels, and exploits the same 6-helix bundle structural motif - in both sodium and calcium channels, this motif is repeated 4 times within the sequence to give a 24-helix bundle. Within each of these repeats, 5 of the transmembrane (TM) segments (S1, S2, S3, S5, S6) are hydrophobic, while the other (S4) is positively charged and serves as the voltage-sensor. Several genes encoding alpha-1 subunits have been identified and can be divided into three functionally distinct families based on sequence homology - Cav1, Cav2 and Cav3 [PMID: 10774722]. The Cav1 family forms channels mediating L-type calcium currents, the Cav2 family mediates P/Q-, N-, and R-type calcium currents, while the Cav3 family mediates T-type calcium currents.
T-type calcium channels exhibit unique voltage-dependent kinetics, small single channel conductance, rapid inactivation, slow deactivation and a relatively high permeability to calcium [PMID: 8815798]. 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 [PMID: 8815798]. They also play an important role in hormone secretion [PMID: 8232302] and smooth muscle excitability [PMID: 2557425].
- PR01629 (TVDCCALPHA1)