Reverse mode of the Na+-Ca2+ exchange after myocardial stretch

Abstract

This study was designed to gain additional insight into the mechanism of the slow force response (SFR) to stretch of cardiac muscle. SFR and changes in intracellular Na<SUP>+</SUP> concentration ([Na<SUP>+</SUP>]<SUB>i</SUB>) were assessed in cat papillary muscles stretched from 92% to ≈98% of L<SUB>max</SUB>. The SFR was 120±0.6% (n=5) of the rapid initial phase and coincided with an increase in [Na<SUP>+</SUP>]<SUB>i</SUB>. The SFR was markedly depressed by Na<SUP>+</SUP>-H<SUP>+</SUP> exchanger inhibition, AT1 receptor blockade, nonselective endothelin-receptor blockade and selective ETA-receptor blockade, extracellular Na<SUP>+</SUP> removal and inhibition of the reverse mode of the Na<SUP>+</SUP>-Ca<SUP>2+</SUP> exchange by KB-R7943. KB-R7943 prevented the SFR but not the increase in [Na<SUP>+</SUP>]<SUB>i</SUB>. Inhibition of endothelin-converting enzyme activity by phosphoramidon suppressed both the SFR and the increase in [Na<SUP>+</SUP>]<SUB>i</SUB>. The SFR and the increase in [Na<SUP>+</SUP>]<SUB>i</SUB> after stretch were both present in muscles with their endothelium (vascular and endocardial) made functionally inactive by Triton X-100. In these muscles, phosphoramidon also suppressed the SFR and the increase in [Na<SUP>+</SUP>]<SUB>i</SUB>. The data provide evidence that the last step of the autocrine-paracrine mechanism leading to the SFR to stretch is Ca<SUP>2+</SUP> entry through the reverse mode of Na<SUP>+</SUP>-Ca<SUP>2+</SUP> exchange.