Activation of reverse Na+-Ca2+ exchanger by skeletal Na+ channel isoform increases excitation-contraction coupling efficiency in rabbit cardiomyocytes

A number of studies suggest that the Na + -Ca 2+ exchanger (NCX) activated by Na + currents is involved in the process of excitation-contraction (EC) coupling in cardiac ventricular myocytes. Although insufficient to trigger sarcoplasmic Ca 2+ release alone, the Ca 2+ entering through reverse NCX during an action potential can prime the dyadic cleft and increase the Ca 2+ current coupling fidelity. Using specific Na + inhibitors in this study, we show that in rabbit ventricular cells the skeletal Na + channel isoform (Na v 1.4) is the main isoform responsible for this priming. Our study provides insights into a mechanism that may have an increased relevance where EC coupling is remodeled.