L-type calcium channels: highs and new lows.

Abstract

Voltage-gated calcium channels are essential for coupling membrane depolarization to the influx of calcium in all excitable cells. The calcium that flows into excitable cells through voltage-gated calcium channels serves a dual function, generating both electrical and chemical signals. The intracellular events controlled by calcium are diverse and many. Excitable cells can select from a number of functionally distinct voltage-gated Ca2+ channel subunits, whose activities are precisely tuned to support specific tasks. These include excitation-contraction coupling in muscle, excitation-secretion coupling in neurons, hair cells, and endocrine cells, and regulation of gene expression.1–5⇓⇓⇓⇓ Ten genes encode the main CaVα1 subunit of the voltage-gated calcium channel complex in mammals.6 Sequence comparisons among CaVα1 genes from several genomes reveal three major families, CaV1α1, CaV2α 1, and CaV3α 1.6 Even before the availability of selective toxins, several investigators demonstrated that multiple, functionally distinct classes of voltage-gated calcium channels are expressed in a variety of cell types including heart.8–11⇓⇓⇓ This division was based on the presence of two distinct classes of calcium channels that differed significantly in their voltage dependence of activation. The concept of low voltage-activated and high voltage-activated calcium channels was established, and although simple, this remains a useful and informative way for distinguishing among different classes of calcium channels. Certain features have emerged from studies of voltage-gated calcium channels in heart and neurons that have established a set of standard criteria to define the presence of a specific Ca2+ channel subtype. Low voltage-activated, T-type, Ca2+ channels that contain CaV3α1 subunits (α1G, α1H, α1I) activate rapidly, deactivate slowly, exhibit pronounced voltage-dependent inactivation, and are insensitive …