Yasuo Mori

Letter to the EditorNomenclature of Voltage-Gated Calcium Channels

As 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 in-alphabetical 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 mem-grouped into three families: (1) ␣ 1S , ␣ 1C , ␣ 1D , and ␣ 1F ; (2) bers of a gene superfamily of transmembrane ion chan-The complete nel proteins that includes voltage-gated K ϩ and Na ϩ amino acid sequences of these ␣ 1 subunits are more channels. The Ca 2ϩ 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 ␣ 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 ge-sites of channel regulation by second messengers, nome. Ideally, a nomenclature for Ca 2ϩ channel ␣ 1 sub-drugs, and toxins. An intracellular ␤ subunit and a trans-units 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 voltage-has 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 nomen-ties 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 sub-channel nomenclature (Chandy et al., 1991). This no-units. Mammalian ␣ 1 …

A New β Subtype-specific Interaction in α1ASubunit Controls P/Q-type Ca2+ Channel Activation

The cytoplasmic β subunit of voltage-dependent calcium channels modulates channel properties in a subtype-specific manner and is important in channel targeting. A high affinity interaction site between the α1 interaction domain (AID) in the I-II cytoplasmic loop of α1 and the β interaction domain (BID) of the β subunit is highly conserved among subunit subtypes. We describe a new subtype-specific interaction (Ss1) between the amino-terminal cytoplasmic domain of α1A (BI-2) and the carboxyl terminus of β4. Like the interaction identified previously (21) between the carboxyl termini of α1A and β4 (Ss2), the affinity of this interaction is lower than AID-BID, suggesting that these are secondary interactions. Ss1 and Ss2 involve overlapping sites on β4 and are competitive, but neither inhibits the interaction with AID. The interaction with the amino terminus of α1 is isoform-dependent, suggesting a role in the specificity of α1-β pairing. Coexpression of β4 in Xenopus oocytes produces a reduced hyperpolarizing shift in the I-V curve of the α1A channel compared with β3 (not exhibiting this interaction). Replacing the amino terminus of α1A with that of α1C abolishes this difference. Our data contribute to our understanding of the molecular organization of calcium channels, providing a functional basis for variation in subunit composition of native P/Q-type channels.