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Am J Physiol Heart Circ Physiol 279: H35-H46, 2000;
0363-6135/00 $5.00
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Vol. 279, Issue 1, H35-H46, July 2000

Coexpression with beta 1-subunit modifies the kinetics and fatty acid block of hH1alpha Na+ channels

Yong-Fu Xiao1,2,4, Sterling N. Wright5, Ging Kuo Wang3,4, James P. Morgan1,4, and Alexander Leaf2,4

1 Charles A. Dana Research Institute and Harvard-Thorndike Laboratory, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, 2 Department of Medicine, Massachusetts General Hospital, and 3 Department of Anesthesia, Brigham and Women's Hospital, 4 Harvard Medical School, Boston, Massachusetts 02215; and 5 Department of Biological Sciences, Murray State University, Murray, Kentucky 42071

Voltage-gated cardiac Na+ channels are composed of alpha - and beta 1-subunits. In this study beta 1-subunit was cotransfected with the alpha -subunit of the human cardiac Na+ channel (hH1alpha ) in human embryonic kidney (HEK293t) cells. The effects of this coexpression on the kinetics and fatty acid-induced suppression of Na+ currents were assessed. Current density was significantly greater in HEK293t cells coexpressing alpha - and beta 1-subunits (INa,alpha beta ) than in HEK293t cells expressing alpha -subunit alone (INa,alpha ). Compared with INa,alpha , the voltage-dependent inactivation and activation of INa,alpha beta were significantly shifted in the depolarizing direction. In addition, coexpression with beta 1-subunit prolonged the duration of recovery from inactivation. Eicosapentaenoic acid [EPA, C20:5(n-3)] significantly reduced INa,alpha beta in a concentration-dependent manner and at 5 µM shifted the midpoint voltage of the steady-state inactivation by -22 ± 1 mV. EPA also significantly accelerated channel transition from the resting state to the inactivated state and prolonged the recovery time from inactivation. Docosahexaenoic acid [C22:6(n-3)], alpha -linolenic acid [C18:3(n-3)], and conjugated linoleic acid [C18:2(n-6)] at 5 µM significantly inhibited both INa,alpha beta and INa,alpha . In contrast, saturated and monounsaturated fatty acids had no effects on INa,alpha beta . This finding differs from the results for INa,alpha , which was significantly inhibited by both saturated and unsaturated fatty acids. Our data demonstrate that functional association of beta 1-subunit with hH1alpha modifies the kinetics and fatty acid block of the Na+ channel.

alpha -subunit; cardiac sodium ion channel; polyunsaturated fatty acids


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