Voltage-Gated Calcium Channels

Voltage-gated calcium channels are heteromultimers composed of an a₁ subunit and three auxiliary subunits, a₂-d, b and g. The a₁ subunit forms the ion pore and possesses gating functions and, in some cases, drug binding sites. Ten a₁ subunits have been identified, which, in turn, are associated with the activities of the six classes of calcium channels. L-type channels have a_1C (cardiac), a_1D (neuronal/endocrine), a_1S (skeletal muscle), and a_1F (retinal) subunits; N-type channels have a_1B subunits; P- and Q-type channels have a_1A subunits, and T-type channels have a_1G, a_1H, and a_1I subunits. The a₁ subunits each have four homologous domains (I-IV) that are composed of six transmembrane helices. The fourth transmembrane helix of each domain contains the voltage-sensing function. The four a₁ domains cluster in the membrane to form the ion pore. The b-subunit is localized intracellularly and is involved in the membrane trafficking of a₁ subunits. The g-subunit is a glycoprotein having four transmembrane segments. The a₂ subunit is a highly glycosylated extracellular protein that is attached to the membrane-spanning d-subunit by means of disulfide bonds. The a₂-domain provides structural support required for channel stimulation, while the d domain modulates the voltage-dependent activation and steady-state inactivation of the channel.

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References:

Jones, S.W., Overview of voltage-dependent calcium channels. J. Bioenerg. Biomembr., 30, 299-312 (1998).