Abstract
In shark heart, the Na super(+)-Ca super(2+) exchanger serves as a major pathway for both Ca super(2+) influx and efflux, as there is only rudimentary sarcoplasmic reticulum in these hearts. The modulation of the exchanger by a beta -adrenergic agonist in whole-cell clamped ventricular myocytes was compared with that of the Na super(+)-Ca super(2+) exchanger blocker KB-R7943. Application of 5 mu M isoproterenol and 10 mu M KB-R7943 suppressed both the inward and the outward Na super(+)- Ca super(2+) exchanger current (I sub(Na-Ca)). The isoproterenol effect was mimicked by 10 mu M forskolin. Isoproterenol and forskolin shifted the reversal potential (E sub(rev)) of I sub(Na-Ca) by approximately -23 mV and -30 mV, respectively. An equivalent suppression of outward I sub(Na-Ca) by KB-R7943 to that by isoproterenol produced a significantly smaller shift in E sub(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 sub(rev) with isoproterenol results from the enhanced efficacy of Ca super(2+) efflux via the exchanger. The protein kinase A-mediated bimodal regulation of the exchanger in parallel with phosphorylation of the Ca super(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 super(2+) release stores.