Voltage-gated Ca2؉ channels in vertebrates comprise at least seven molecular subtypes, each of which produces a current with distinct kinetics and pharmacology. Voltage-gated Ca 2ϩ channels are essential for coupling the depolarization of excitable cells to Ca 2ϩ influx across the plasma membrane, leading to initiation of second messenger cascades and other intracellular events. The various voltagegated Ca 2ϩ currents that have been described in vertebrate and invertebrate tissues were originally defined by their biophysical and pharmacological differences. Isolation of cDNAs encoding several mammalian Ca 2ϩ channel subtypes has provided a molecular basis for the diversity of Ca 2ϩ currents in higher vertebrates (for review see Refs. 1 and 2). Mammalian Ca 2ϩ channels are composed of a pore-forming ␣ 1 subunit and associated  and ␣ 2 ␦ subunits, as well as a ␥ subunit specific to skeletal muscle. Although the accessory subunits play important roles in channel modulation (3-5), the ␣ 1 subunit is primarily responsible for determining the pharmacology and physiology of the resulting current, and heterologous expression of cloned vertebrate ␣ 1 subunits has allowed correlation between molecular subtypes and native currents. L-type currents, sensitive to 1,4-dihydropyridines (DHPs), 1 are gated by the ␣ 1S subtype found in skeletal muscle (6) and the ␣ 1C (3) and ␣ 1D (7) subtypes expressed in heart, brain, and other tissues. DHP-insensitive, non-L-type ␣ 1 subunits include the ␣ 1B subtype, which is responsible for the -conotoxin GVIA-sensitive N-type current (8), the ␣ 1A subtype, which gates the -agatoxin IVA-sensitive P/Q-type current (9), and ␣ 1E , which gates R-type currents (10). In addition to these high voltage-activated (HVA) ␣ 1 subunits, the ␣ 1G subunit, responsible for the low voltageactivated (LVA) T-type current, has recently been cloned and characterized (11).Comparison of the primary structures of the six identified vertebrate HVA ␣ 1 subtypes reveals a distinct separation between the L-type and non-L-type channel subfamilies. The similarity among subunits within each class is greater than that between the classes, suggesting that divergence between L-type and non-L-type channels constituted the first step in the evolution of known HVA Ca 2ϩ channels. This division between channel classes is maintained in the invertebrate Ca 2ϩ channels that have been cloned (for review see Ref. 12). Single homologues of both L-type and non-L-type channels have been found in Drosophila (13,14) and Aplysia (15), and other invertebrate Ca 2ϩ channel sequences (16 -18) exhibit clear resemblance to one of the two channel subfamilies. However, a thorough understanding of the relationship between invertebrate Ca 2ϩ channel structure and physiology requires functional expression of a cloned invertebrate Ca 2ϩ channel ␣ 1 subunit. Cnidarians, which include jellyfish, anemones, and corals, are the earliest existing organisms to possess a neuromuscular system. Voltage-gated Ca 2ϩ currents have been recorded from neural and...