PHARMACOLOGICAL ANALYSIS OF HEARTBEAT IN DROSOPHILA

Analysis of the mechanisms underlying cardiac excitability can be faci litated greatly by mutations that disrupt ion channels and receptors i nvolved in this excitability. With an extensive repertoire of such mut ations, Drosophila provides the best available genetic model for these studies. However, the use of Drosophila for this purpose has been sev erely handicapped by lack of a suitable preparation of heart and a com plete lack of knowledge about the ionic currents that underlie its exc itability. We describe a simple preparation to measure heartbeat in Dr osophila, This preparation was used to ask if heartbeat in Drosophila is myogenic in origin, and to determine the types of ion channels invo lved in influencing the heart rate. Tetrodotoxin, even at a high conce ntration of 40 mu M, did not affect heart rate, indicating that heartb eat may be myogenic in origin and that it may not be determined by Na channels. Heart rate was affected by PN200-110, verapamil, and diltia zem, which block vertebrate L-type Ca2+ channels. Thus, L-type channel s, which contribute to the prolonged plateau of action potentials in v ertebrate heart, may play a role in Drosophila cardiac excitability. I t also suggests that Drosophila heart is subject to a similar interven tion by organic Ca2+ channel blockers as the vertebrate heart. A role for K+ currents in the function of Drosophila heart was suggested by a n effect of tetraethylammonium, which blocks all the four identified K + currents in the larval body wall muscles, and quinidine, which block s the delayed rectifier K+ current in these muscles, The preparation d escribed here also provides an extremely simple method for identifying mutations that affect heart rate, Such mutations and pharmacological agents will be very useful for analyzing molecular components of cardi ac excitability in Drosophila. (C) 1995 John Wiley & Sons, Inc.