Roles of the Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase, Plasma Membrane Ca2+-ATPase and Na+/Ca2+ Exchanger in Regulation of Heart Rate in Larval Drosophila

摘要

We investigated the roles of three regulatory proteins that impact [Ca2+]i within cardiac myocytes ofDrosophila melanogaster. The NCX (Na+/Ca2+ exchanger), PMCA (plasma membrane Ca2+-ATPase) and SERCA(sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) were compromised by ionic, pharmacological, mutationalmanipulation,and with a combination of approaches, while heart rate (HR) was monitored. A decrease in SERCAfunction reduced HR more for intact larva in comparison to a dissected larva. Dissected preparations were used to exposethe heart directly to agents. A compromised PMCA also reduced HR; however, attenuated NCX function by low [Na+]○increased HR. KBR7943, a blocker of Ca2+ entry via NCX, exposure increased HR. A combined loss of function in allthree channels did not show a significant change in HR. The results indicate that NCX and PMCA are important inregulating HR, whereas SERCA does not have as pronounced role for dissected preparations. However, with intactpreparations the loss of SERCA function by a mutation does have a significant impact on HR. Pharmacologicalapproaches to alter PMCA and SERCA paralleled the results obtained by ionic and mutational approaches. To furtherunderstand the pacemaker activity, intracellular recordings were obtained. Mapping of action-potentials in myocytesrevealed that the caudal region of the heart has large amplitude potentials and is likely to contain the pacemaker cells. TheDrosophila heart can serve as a genetic model in understanding regulation of ionic currents for pacing cells of various types.