Calcium Channels: Structure and Function (Annals of the New York Academy of Sciences. Volume 560)

Much attention has been directed towards voltage-sensitive ion channels selective for calcium ions because of their important physiological roles in cell signaling. The development of patch-clamping techniques, has facilitated detailed study of the functional properties of single calcium channels. Parallel biochemical advances, achieved by using radio labeled calcium channel ligands and more recently cloned DNA techniques, have led to insights into the structural and molecular properties of calcium channels. Classification of calcium channels into subtypes has been on the basis of their electrophysiological and pharmacological properties. Subtypes have been differentiated according to their voltage threshold for activation and by their inactivation characteristics low threshold inactivating T, dihydropyridine- sensitive high-threshold non-inactivating L, and high-threshold inactivating N. Electrophysiological experiments have studied gating and ion selectivity a calcium channels. Because of its relative abundance and sensitivity to dihydropyridines, the L-type calcium channel from skeletal muscle was the first to be purified, and its molecular properties and oligomeric structure are now well characterized. Newer radiolabeled calcium channel drugs are becoming available. Benzothiazepines, phenylalkylamines, and dihydropyridines bind to three allosterically coupled binding sites on the a1 subunit. Other calcium channel ligands such as monoclonal as well as polyclonal antibodies are proving to be valuable probes against the channel.