Functional differences between cardiac and renal isoforms of the rat Na+-Ca2+ exchanger NCX1 expressed in Xenopus oocytes

1. The transcript of the Na+-Ca2+ exchanger gene NC;SII undergoes alternati ve splicing to produce tissue-specific isoforms. The cloned NCX1 isoforms w ere expressed in Xenopus oocytes and studied using a two-electrode voltage clamp method to measure Na+-Ca2+ exchanger activity. 2. The cardiac isoform (NCX1.1) expressed in oocytes was less sensitive to depolarizing voltages and to activation by [Ca2+](i) than the renal isoform (NCX1.3). 3. The cardiac isoform of NCX1 is more sensitive to activation by protein k inase A (PKA) than the renal isoform which may be explained by preferential phosphorylation. The cardiac isoform of NCX1 is phosphorylated to a greate r extent than the renal isoform. 4. The action of PKA phosphorylation which increases the activity of the ca rdiac isoform of the Na+-Ca2+ exchanger in oocytes was confirmed in adult r at ventricular cardiomyocytes by measuring Na+-dependent Ca2+ flux. 5. We conclude that alternative splicing of NCX1 confers distinct functiona l characteristics to tissue-specific isoforms of the Na+-Ca2+ exchanger.