As new Ca2+ channel genes are cloned, it is apparent that these two alphabetical nomenclatures will overlap at α1L, which may not mediate an L-type Ca2+ current and Voltage-gated Ca2+ channels mediate calcium influx in therefore may create confusion. Moreover, the present response to membrane depolarization and regulate in- alphabetical nomenclature does not reveal the structural tracellular processes such as contraction, secretion, relationships among the α1 subunits, which can be neurotransmission, and gene expression. They are mem- grouped into three families:(1) α1S, α1C, α1D, and α1F;(2) bers of a gene superfamily of transmembrane ion chan- α1A, α1B, and α1E; and (3) α1G, α1H, and α1I. The complete nel proteins that includes voltage-gated K+ and Na+ amino acid sequences of these α1 subunits are more channels. The Ca2+ channels that have been character- than 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 α1 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 Ca2+ channel α1 subdrugs, and toxins. An intracellular ß subunit and a trans- units should provide a systematic organization based on membrane, disulfide-linked α2δ subunit complex are their structural relationships and should be coordinated components of most types of Ca2+ channels. A subunit with nomenclatures for the other families of voltagehas also been found in skeletal muscle Ca2+ channels, gated ion channels of different ionic selectivities (ie., K+ and related subunits are expressed in heart and brain. and Na+). 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 Ca2+ channels (Table 1), which electrophysiological diversity of Ca2+ channels arises is more systematic and mimics the well-defined K+ primarily from the existence of multiple forms of α1 sub- channel nomenclature (Chandy et al., 1991). This nounits. Mammalian α1 subunits are encoded by at least menclature uses a numerical system (KV1. 1, KV2. 1, KV3. 1, ten distinct genes. Historically, various names have etc.) to define families and subfamilies of K+ channels been given to the corresponding gene products, giving based on similarities in amino acid sequences. In a simirise to distinct and sometimes confusing nomencla- lar manner, we propose that Ca2+ channels should be tures. In 1994, some of us proposed a unified nomencla- renamed using the chemical symbol of the principal ture based on the most widely accepted system at the permeating ion (Ca) with the principal physiological regtime: α1 subunits were referred to as α1S for the original ulator (voltage) indicated as a subscript (CaV). The nuskeletal muscle isoform and α1A through α1E for those merical identifier would correspond to the CaV channel discovered subsequently (Birnbaumer et al., 1994). α1 subunit gene family (1 through 3 at present) and the Since then, four new α1 subunits have been identified, order of discovery of the α1 subunit within that family (1 which were named α1F through α1I.

Ca2+ currents …