Species Differences and the Role of Sodium‐Calcium Exchange in Cardiac Muscle Relaxation^a

Abstract

During normal relaxation in rabbit, guinea-pig, and rat ventricular muscle, the Na-Ca exchange system competes with the SR Ca pump, with the former being responsible for about 20-30% of the Ca removal from the cytoplasm. Ca extrusion via Na-Ca exchange is Em-sensitive, whereas Ca uptake by the SR is not. Neither the sarcolemmal Ca-ATPase pump nor mitochondrial Ca uptake appear to contribute significantly to the decline of [Ca]i during relaxation. Furthermore, the diastolic efflux of Ca from cardiac muscle cells appears to be primarily attributable to Na-Ca exchange and not the sarcolemmal Ca-ATPase pump. In rabbit ventricle Ca entry via Na-Ca exchange is favored thermodynamically during much of a normal twitch contraction and Ca extrusion occurs primarily between beats. In rat ventricle Ca efflux via Na-Ca exchange occurs during the contraction and net Ca influx may occur between beats. This fundamental difference in Ca fluxes during the cardiac cycle in rat versus rabbit ventricle may be a simple consequence of the shorter action potential duration and higher aNai in rat ventricle (due to the effects of Em and [Na] and [Ca] gradients on Na-Ca exchange).

Calcium dependency of frequency-stimulated atrial natriuretic peptide secretion.

“…Developed tension and peak systolic [Ca 2+ ] ( fall with increased frequency (in the frequency range we examined) in rat cardiac tissue, 33 which distinguishes it from other species. 34 - 35 This may be due to the observation that calcium efflux is predominant during systole via the Na + -Ca 2+ exchanger, whereas in other species calcium influx is greater than efflux during systole. 35 The reverse is true during diastole, during which calcium influx predominates in rat cardiac tissue.…”

“…34 - 35 This may be due to the observation that calcium efflux is predominant during systole via the Na + -Ca 2+ exchanger, whereas in other species calcium influx is greater than efflux during systole. 35 The reverse is true during diastole, during which calcium influx predominates in rat cardiac tissue. As the contraction frequency is increased, diastole shortens, which decreases the time allowed for SR calcium repletion.…”

“…As the contraction frequency is increased, diastole shortens, which decreases the time allowed for SR calcium repletion. 35 Thus, as SR calcium stores are reduced, developed tension and peak systolic [Ca 2+ ], fall. However, a recent study reports a rise in systolic [Ca 2+ ]| and enhanced contraction with increased beat frequency in isolated rat cardiac cells.…”

Overexpression of the Na/Ca Exchanger Shapes Stimulus-Induced Cytosolic Ca2+ Oscillations in Insulin-Producing BRIN-BD11 Cells

“…The Na/Ca exchanger is an electrogenic transporter located at the plasma membrane that couples the exchange of Na ϩ and Ca 2ϩ with a stoichiometry of three Na ϩ for one Ca 2ϩ (7). In the cardiac myocyte, Na/Ca exchange is the major mechanism of Ca 2ϩ extrusion, restoring basal Ca 2ϩ levels between heartbeats (8). The exchanger may also reverse during the heart cycle and hence allow Ca 2ϩ entry during the systole (9).…”

Phosphorylation-dependent Regulation of Cardiac Na+/Ca2+ Exchanger via Protein Kinase C

“…In cardiac muscle, this exchanger is particularly important in that during each action potential it rapidly extrudes the Ca 2ϩ that has entered the cardiomyocytes via the sarcolemmal L-type Ca 2ϩ channels to trigger the release of Ca 2ϩ from the sarcoplasmic reticulum (SR) 1 (1,2). In addition, the Na ϩ /Ca 2ϩ exchanger has been shown to play a much greater role in the slow extrusion of Ca 2ϩ from cardiomyocytes during diastole or under resting conditions than the sarcolemmal Ca 2ϩ pump (1,3). The same exchanger, on the other hand, is capable of bringing Ca 2ϩ into cardiomyocytes during cardiac depolarization, although triggering the release of Ca 2ϩ from the SR is much less efficient than that via the L-type Ca 2ϩ channels (1,4).…”