Bimodal regulation of Na~+--Ca~2+ exchanger by β-adrenergic signaling pathway in shark ventricular myocytes

摘要

In shark heart, the Na~+--Ca~2+ exchanger serves as a major pathway for both Ca~2+ influx and efflux. as there is only rudimentary sarcoplasmic reticulum in these hearts. The modulation of the exchanger by a β-adrenergic agonist in whole-cell clamped ven- tricular myocytes was compared with that of the Na~+--Ca~2+ ex- changer blocker KB-R7943. Application of 5 μM isoproterenol and 10 μM KB-R7943 Suppressed both the inward and the outward Na~+--Ca~2+ exchanger current (I_Na-Ca). The isoproterenol effect was mimicked by 10 μM forskolin. Isoproterenol and forskolin shifted the reversal potential (E_rev) of I_Na-Ca by approximately --23 mV and --30 mV. respectively. An equivalent suppression of outward IN.--c. by KB-R7943 to that by isoproterenol produced a significantly smaller shift in E_rev of about --4 mV. The ratio of inward to outward exchanger currents was also significantly larger in isoproterenol- than in control- and KB-R7943-treated myocytes. Our data suggest that the larger ratio of inward to outward exchanger currents as well as the larger shift in E_rev with isoproterenol results from the enhanced efficacy of Ca~2+ efflux via the exchanger. The protein kinase A-mediated bimodal regulation of the exchanger in parallel with phosphorylation of the Ca~2+ channel and enhancement of its current may have evolved to satisfy the evolutionary needs for accelerated contraction and relaxation in hearts of animals with vestigial sarcoplasmic Ca~2+ release stores.