Functional differences between cardiac and renal isoforms of the rat Na+-Ca2+ exchanger NCX1 expressed in Xenopus oocytes.
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
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Department of Microbiology and Immunology, Department of Physiology and Medical Biotechnology Center, UMBI, University of Maryland at Baltimore, School of Medicine, Baltimore, MD 21201, USA. aruknudi@umaryland.edu
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Lederer
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Schulze
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D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004553:Electric Conductivity; D004789:Enzyme Activation / Q000502:physiology; D007668:Kidney / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000378:metabolism* / Q000502:physiology; D014981:Xenopus
D020033:Protein Isoforms; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D017868:Cyclic AMP-Dependent Protein Kinases