RESOLUTION AND PHARMACOLOGICAL ANALYSIS OF THE VOLTAGE-DEPENDENT CALCIUM CHANNELS OF DROSOPHILA LARVAL MUSCLES

Voltage-dependent calcium channels play a role in many cellular phenom ena. Very little is known about Ca2+ channels in Drosophila, especiall y those in muscles. Existing literature on neuronal Ca2+ channels of D rosophila suggests that their pharmacology may be distinct from that o f vertebrate Ca2+ channels. This raises questions on the pharmacology and diversity of Ca2+ channels in Drosophila muscles. Here we show tha t the Ca2+ channel current in the body-wall muscles of Drosophila larv ae consists of two main components. One component is sensitive to 1,4- dihydropyridines and diltiazem, which block vertebrate L-type Ca2+ cha nnels. The second component is sensitive to amiloride, which blocks ve rtebrate T-type Ca2+ channels. In contrast to Drosophila brain membran e preparations in which a majority of the Ca2+ channels are phenylalky lamine-sensitive but dihydropyridine-insensitive, the major current in the muscles was dihydropyridine-sensitive but relatively less sensiti ve to verapamil. This might indicate an underlying tissue specific dis tribution of distinct subtypes of dihydropyridine/phenylalkylamine-sen sitive Ca2+ channels in Drosophila. Low verapamil sensitivity of the d ihydropyridine-sensitive current of Drosophila muscles also set it apa rt from the vertebrate L-type channels which are sensitive to 1,4-dihy dropyridines, benzothiazepines as well as phenylalkylamines. The dihyd ropyridine-sensitive current in Drosophila muscles activated in a simi lar voltage range as the vertebrate L-type current. As with the verteb rate current,; blockade by dihydropyridines was voltage dependent. Com pared to the vertebrate T-type current, the amiloride-sensitive curren t in Drosophila muscles showed higher activation threshold as well as slower inactivation. These experiments provide the first clear resolut ion of a Drosophila Ca2+ current into two distinct components. With th e previous resolution of the K+ current into four components, Drosophi la larval muscles now provide one of the few preparations in which the whole cell current can be resolved completely into individual ionic c urrents. This will help in determining the role of individual currents in cellular excitability and other calcium related processes; in anal yzing structure, function, and regulation of specific types of Ca2+ ch annels; as well as in understanding the molecular basis of calcium cha nnel diversity.