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Title of article :
Late Na Currents Affected by α Subunit Isoform and β1 Subunit Co-expression in HEK293 Cells
Author/Authors :
Carmen R. Valdivia، نويسنده , , Toshihisa Nagatomo، نويسنده , , Jonathan C. Makielski، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2002
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Abstract :
C. R. Valdivia, T. Nagatomo and J. C. Makielski. Late Na Currents Affected by α Subunit Isoform and β1 Subunit Co-expression in HEK293 Cells. Journal of Molecular and Cellular Cardiology (2002) 34, 1029–1039. Peak Na current underlies excitability and conduction in the heart, and late non-inactivating or slowly inactivating Na current plays a role in action potential duration. We hypothesized that different α subunit isoforms or β1 subunit co-expression might affect late Na current. The human Na channel α subunits hNav1.5 (hH1a) and hNav1.4 (hSkM1) were transfected with and without the hNaVβ1 (β1) subunit in HEK293 cells and studied by whole cell patch clamp. The inactivation relationship for hH1a was 28 mV negative to that for hSkM1, and β1 shifted the midpoint positively by 22 mV for hH1a and 8 mV for hSkM1. When pre-pulse duration was varied from 10 ms to 10 s, “steady-state” was approached more slowly for hH1a. β1 caused hH1a but not hSkM1 to reach “steady-state” earlier. Both isoforms showed two recovery components but hH1a showed a “cardiac phenotype” with a smaller slow component that was unaffected by β1. The amplitude of a late current (at 750 ms) was significantly greater for hH1a than hSkM1, but β1 decreased late current for hH1a and eliminated the difference. Under the study conditions the α subunit isoforms have distinct functional phenotypes and co-expression with β1 tends to diminish these distinctions. These properties may provide mechanisms for regional and transmural distribution of late Na current and late Na current amplitudes during development and in disease states.
Keywords :
SCN5A , SCN4A , Voltage gated sodium channels , Channel isoforms. , Inactivation kinetics
Journal title :
Journal of Molecular and Cellular Cardiology
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