Functional differences between cardiac and renal isoforms of the rat Na + ‐Ca 2+ exchanger NCX1 expressed in Xenopus oocytes

1 The transcript of the Na + ‐Ca 2+ exchanger gene NCX1 undergoes alternative splicing to produce tissue‐specific isoforms. The cloned NCX1 isoforms were expressed in Xenopus oocytes and studied using a two‐electrode voltage clamp method to measure Na + ‐Ca 2+ exchanger activity. 2 The cardiac isoform (NCX1.1) expressed in oocytes was less sensitive to depolarizing voltages and to activation by [Ca 2+ ] i than the renal isoform (NCX1.3). 3 The cardiac isoform of NCX1 is more sensitive to activation by protein kinase A (PKA) than the renal isoform which may be explained by preferential phosphorylation. The cardiac isoform of NCX1 is phosphorylated to a greater extent than the renal isoform. 4 The action of PKA phosphorylation which increases the activity of the cardiac isoform of the Na + ‐Ca 2+ exchanger in oocytes was confirmed in adult rat ventricular cardiomyocytes by measuring Na + ‐dependent Ca 2+ flux. 5 We conclude that alternative splicing of NCX1 confers distinct functional characteristics to tissue‐specific isoforms of the Na + ‐Ca 2+ exchanger.