Voltage-dependent calcium channel, L-type, beta-3 subunit (IPR008079)
Short name: VDCC_L_b3su
Overlapping homologous superfamilies
- Voltage-dependent calcium channel, L-type, beta subunit (IPR000584)
- Voltage-dependent calcium channel, L-type, beta-3 subunit (IPR008079)
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.
Co-expression of beta subunit mRNA with alpha-1 subunit mRNA in xenopus oocytes produces increased calcium currents, which are accompanied by a shift in the voltage-dependence of activation to more negative membrane potentials. Conversely, microinjection of antisense oligonucleotides to beta subunit mRNA produces decreased calcium currents and shifts voltage-dependent activation to more positive membrane potentials. There are four distinct beta subunits: beta-1, beta-2, beta-3 and beta-4; and the magnitude of the shift in the voltage-dependence of activation of change to membrane potentials varies with the particular subtype [PMID: 9153247].
Beta-3 subunits are most abundant in the brain, but are also present in aorta, trachea, lung, heart, skeletal muscle and pancreatic islets, where they play a role in the regulation of insulin secretion [PMID: 7679112]. The beta-3 subunits regulate the activation (opening) and inactivation (closing) kinetics through phosphorylation and dephosphorylation. However, it is noted that no single channel is dependent on the beta-3 subunit.
- PR01696 (LCACHANNELB3)