Nomenclature of Voltage-Gated Calcium Channels

Abstract

Letter to the Editorshaping the action potential and controlling patterns of Nomenclature of Voltage-Gated repetitive firing. Calcium ChannelsAs new Ca 2ϩ channel genes are cloned, it is apparent that these two alphabetical nomenclatures will overlap at ␣ 1L , which may not mediate an L-type Ca 2ϩ current and Voltage-gated Ca 2ϩ channels mediate calcium influx in therefore may create confusion. Moreover, the present response to membrane depolarization and regulate inalphabetical nomenclature does not reveal the structural tracellular processes such as contraction, secretion, relationships among the ␣ 1 subunits, which can be neurotransmission, and gene expression. They are memgrouped into three families: (1) ␣ 1S , ␣ 1C , ␣ 1D , and ␣ 1F ; (2) bers of a gene superfamily of transmembrane ion chan-␣ 1A , ␣ 1B , and ␣ 1E ; and (3) ␣ 1G , ␣ 1H , and ␣ 1I . The complete nel proteins that includes voltage-gated K ϩ and Na ϩamino acid sequences of these ␣ 1 subunits are more channels. The Ca 2ϩ channels that have been characterthan 70% identical within a family but less than 40% ized biochemically are complex proteins composed of identical among families. These family relationships are four or five distinct subunits, which are encoded by illustrated for the more conserved transmembrane and multiple genes. The ␣ 1 subunit of 190-250 kDa is the pore domains in Figure 1. Division of calcium channels largest subunit, and it incorporates the conduction pore, into these three families is phylogenetically ancient, as the voltage sensor and gating apparatus, and the known representatives of each are found in the C. elegans gesites of channel regulation by second messengers, nome. Ideally, a nomenclature for Ca 2ϩ channel ␣ 1 subdrugs, and toxins. An intracellular ␤ subunit and a transunits should provide a systematic organization based on membrane, disulfide-linked ␣ 2 ␦ subunit complex are their structural relationships and should be coordinated components of most types of Ca 2ϩ channels. A ␥ subunit with nomenclatures for the other families of voltagehas also been found in skeletal muscle Ca 2ϩ channels, gated ion channels of different ionic selectivities (ie., K ϩ and related subunits are expressed in heart and brain. and Na ϩ ). Although these auxiliary subunits modulate the proper-For these reasons, we wish to propose a new nomenties of the channel complex, the pharmacological and clature of voltage-gated Ca 2ϩ channels (Table 1), which electrophysiological diversity of Ca 2ϩ channels arises is more systematic and mimics the well-defined K ϩ primarily from the existence of multiple forms of ␣ 1 subchannel nomenclature (Chandy et al., 1991). This nounits. Mammalian ␣ 1 subunits are encoded by at least menclature uses a numerical system (K V 1.1, K V 2.1, K V 3.1, ten distinct genes. Historically, various names have etc.) to define families and subfamilies of K ϩ channels been given to the corresponding gene products, giving based on similarities in amino acid sequences. In a simirise to distinct and sometimes confusing nome...

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