GENETIC AND PHARMACOLOGICAL IDENTIFICATION OF ION CHANNELS CENTRAL TOTHE DROSOPHILA CARDIAC-PACEMAKER

Drosophila provides an excellent model for delineating the role of ion channels in the origin and transmission of heartbeat. We report here tests in Drosophila on a wide range of mutations and pharmacological a gents known to interfere with K+, Ca2+, Na+, and Cl- ion channels in w ell-characterized ways. We find K+ channels are central to heart funct ion. Tetraethylammonium, which blocks all four K+ currents, slowed the heart. We were able to distinguish among these currents. The mutation slowpoke and the agent charybdotoxin, both of which affect a fast Ca2 +-gated K+ channel, virtually eliminate heartbeat. Shaker and ether-a- go-go, which encode subunits of K+ channels, have moderate, possibly r egulatory effects. ''OPQ-type'' Ca2+ channels are critical. omega-Cono toxin MVIIC, which blocks these channels, virtually stops the heart. A miloride, which may affect T-type Ca2+ channels, has no effect, nor do the L-type Ca2+ blockers verapamil and diltiazem. temperature induced paralysis E, involved in the function of Na+ channels, the Na+ channe l blockers tetrodotoxin and amiloride, and the Cl- blockers mefanamic and niflumic acids have no effect. Na+ and Cl- channels thus appear un necessary for cardiac function.