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

Abdul Ruknudin*†, Suiwen He*, W. J. Lederer†‡ and Dan H. Schulze*

1. 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.

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 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⁺-Ca²⁺ exchanger in oocytes was confirmed in adult rat ventricular cardiomyocytes by measuring Na⁺-dependent Ca²⁺ flux.

5. We conclude that alternative splicing of NCX1 confers distinct functional characteristics to tissue-specific isoforms of the Na⁺-Ca²⁺ exchanger.

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