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

摘要

class="enumerated" style="list-style-type:decimal">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.