Coexpression with β1-subunit modifies the kinetics and fatty acid block of hH1α Na+ channels

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 (hH1(alpha)) 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 (I-Na,I-alpha beta) than in HEK293t cells expressing alpha-subunit alone (I-Na,I-alpha). Compared with I-Na,I-alpha, the voltage-dependent inactivation and activation of I-Na,I-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 I-Na,I-alpha beta in a concentration-dependent manner and at 5 mu M 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 mu M significantly inhibited both I-Na,I-alpha beta and I-Na,I-alpha. In contrast, saturated and monounsaturated fatty acids had no effects on I-Na,I-alpha beta. This finding differs from the results for I-Na,I-alpha, which was significantly inhibited by both saturated and unsaturated fatty acids. Our data demonstrate that functional association of beta(1)-subunit with hH1(alpha) modifies the kinetics and fatty acid block of the Na+ channel.