The cardiac isoform of the Na+-Ca2+ exchanger (NCX1.1) is less sensitive to depolarizing voltages and intracellular calcium, but more sensitive to PKA activation than the renal isoform (NCX1.3).
Alternative splicing of the NCX1 gene confers distinct functional characteristics to tissue-specific isoforms, with the cardiac isoform showing greater sensitivity to PKA activation.
The transcript of the Na+-Ca2+ 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+-Ca2+ exchanger activity. 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). 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. The action of PKA phosphorylation which increases the activity of the cardiac isoform of the Na+-Ca2+ exchanger in oocytes was confirmed in adult rat ventricular cardiomyocytes by measuring Na+-dependent Ca2+ flux. We conclude that alternative splicing of NCX1 confers distinct functional characteristics to tissue-specific isoforms of the Na+-Ca2+ exchanger.
Ruknudin et al. (2000) studied this question. Cardiac isoform (NCX1.1) expression vs. Renal isoform (NCX1.3) expression was evaluated on Na+-Ca2+ exchanger activity. The cardiac isoform of the Na+-Ca2+ exchanger (NCX1.1) is less sensitive to depolarizing voltages and intracellular calcium, but more sensitive to PKA activation than the renal isoform (NCX1.3).
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