Invited Symposium: Molecular Physiology of Sodium-Calcium Exchange
Ion transport and regulation were examined for two alternatively spliced isoforms of the NCX1 Na-Ca exchanger. These exchangers, NCX1.3 and NCX1.4, are commonly refered to as the kidney and brain isoforms and express the BD and AD exons, respectively. Alternative exon expression occurs towards the C-terminus of the large cytoplasmic loop. These exchangers differ only in the expression of the A or B exon, thus permitting assessment of the role(s) of these two mutually exclusive exons. Na-Ca exchange activity was examined using giant excised membrane patches from Xenopus laevis oocytes expressing the cloned exchangers. No differences were seen in the current-voltage relationships of outward exchange currents whereas there were large differences in ionic regulation between these exchangers. Na-dependent regulation was considerably more pronounced for the kidney exchanger (NCX1.3) resulting in substantial inhibition of steady state currents compared to the brain exchanger (NCX1.4). By all criteria examined, the Na-dependent inactive state was more stable for the kidney exchanger. Regulatory Ca showed minimal effects on Na-dependent inactivation of NCX1.3 whereas it could completely eliminate this inactivation for NCX1.4, similar to the cardiac Na-Ca exchanger (NCX1.1). These results establish a major role for the alternative splicing region in affecting ionic regulation of mammalian Na-Ca exchange activity.
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|Hryshko, LV; (1998). Functional Differences In NCX1 Sodium-Calcium Exchanger Splice Variants From Kidney And Brain. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/lytton/hryshko0740/index.html|
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