Neuron, Vol. 13, 505-506, September, 1994, Copyright © 1994 by Cell Press Matters Arising The Naming of Voltage-Gated Calcium Channels Voltage-gated calcium channels are multisubunit complexes formed of a central channel-forming a, sub- unit and several regulatory and/or auxiliary subunits which include a ȕ subunit and the disulfide-linked α2δ subunit. Depending on the tissue of origin, a fifth sub- unit, such as the skeletal muscle Ȗ or the neuronal p95, may also form part of the channel complex. Additional subunits may still be discovered. Molecular cloning has greatly expanded the understanding of calcium channel diversity, but confusion remains in the naming of the plethora of genes that encode calcium channel α1 and ȕ subunits. This is further complicated by the fact that the transcripts of most subunits are subject to alterna- tive splicing, which in some but not all cases, may be tissue specific. Table 1 compares the names of cloned α1 genes and their mature mRNAs, their major sites of known expression, and their functional correlates as they are perceived today. Table 2 lists ȕ subunit genes splice variants, and some sites of expression. To simplfy matters, the undersigned propose to use a unified nomenclature based on rules that allow the description of a mature assembled heteromeric channel in terms of an α1XȕnȖn · α2δn complex, where X is a capital letter (S, A, B, C, D, E, etc.) that identifies the genes from which the α1 subunit originates, and n is a number (1, 2, 3, etc.) that identifies the genes from which other calcium channel subunits originate. α1S denotes the α1 subunit of the skeletal muscle calcium channel, the first of theses channels to be cloned in the laboratory of the late Professor Shosaku Numa. α1A through α1E denote the α1 subunits cloned subsequently, labeled with an Table 1. Calcium Channel α1 Subunits Gene Product Functional Correlates Consensus Name(s) Original Name(s) if Different Sites of Expression Current Drug Sensitivity of Native Currents α1S Skeletal muscle HVA L type Sensitive to DHPs, diltiazem and verapamil CaCh1 Skeletal muscle, BC3H1 cells α1skm Insensitive to sub-µM ω-CTx-GVIA and funnel web spider venoms (ω-Aga-IVA, FTX) α1A HVA Q type? ω-CTx-MVIIC (>100 nM); ω-CTx-G Bl CaCh4 Brain, cerebellum, Purkinje and granule cells, kidney, DHP insensitive rbA PC12 cells, C cells HVA P type? Sensitive to ω-Aga-IVA (<10nM) and low sFTX DHP insensitive α1B Blll Brain, peripheral HVA N type CaCh5 neurons, PC12 cells, Sensitive to ω-CTx-GVIA (100-500 nM) and ω-CTx-MVIIC (>100 nM) rbB C cells DHP insensitive α1C Cardiac Smooth muscle/ lung Heart, HIT cells, GH3 cells, brain, aorta, lung, kidney, fibroblasts HVA L type DHP sensitive Insensitive to low concentrations of ω-CTx-GVIA, ω-Aga-IVA, or sFTX CaCh2 PC12 cells, C cells rbC α1C-a CaCh2a Heart CaCh2-I α1C-b CaCh2b Smooth muscle, lung CaCh2-II α1C-c rbC Brain CaCh2-III α1D CaCh3 Brain, pancreas, HIT HVA L type DHP sensitive Neuroendocrine rbD cells, GH3 cells, PC12 cells, C cells Reversibly sensitive to ω-CTx-GVIA, ω-Aga-IVA, or FTX α1E CaCh6 Brain, heart, C cells HVA R type? Sensitive to low Ni BII rbE Insensitive to DHPs or ω-CTx-MVIIC, or to low concentrations of ω-CTx-GVIA, ω-Aga-IVA or sFTX This table in intended as a guide and refers only to mammalian calcium channels. Not all previously used names are listed. Vertebrate doe-1 and doe-4 α1 subunits, cloned from the marine ray Discopyge ommata, are orthologs of mammalian α1E and α1B, respectively. HVA and LVA, high and low voltage activated; DHP, dihydrophyridine; ω-CTx-G and ω-CTx-M, ω-conotoxins from marine snails Conus geographus and Conus magus, respectively; Aga, agatoxin (funnel web spider Agelenopsis aperta toxin); sFTX, synthetic funnel web spider toxin. Q-type calcium channel: current in cerebellar granule cells sensitive to ω-CTx-MVIIC but insensitive to DHPs, low ω-CTx- GVIA, and low ω-Aga-IVA; R-type calcium channel: residual in cerebellar granule cells after blocking with DHP, ω-Aga-IVA, ω-CTx-GVIA, and ω-CTx_MVIIC.