Coexpression with β1-subunit modifies the kinetics and fatty acid block of hH1αNa+channels

Voltage-gated cardiac Na+channels are composed of α- and β1-subunits. In this study β1-subunit was cotransfected with the α-subunit of the human cardiac Na+channel (hH1α) 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 α- and β1-subunits ( INa,αβ) than in HEK293t cells expressing α-subunit alone ( INa,α). Compared with INa,α, the voltage-dependent inactivation and activation of INa,αβwere significantly shifted in the depolarizing direction. In addition, coexpression with β1-subunit prolonged the duration of recovery from inactivation. Eicosapentaenoic acid [EPA, C20:5(n–3)] significantly reduced INa,αβin 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)], α-linolenic acid [C18:3(n–3)], and conjugated linoleic acid [C18:2(n–6)] at 5 μM significantly inhibited both INa,αβand INa,α.In contrast, saturated and monounsaturated fatty acids had no effects on INa,αβ. This finding differs from the results for INa,α, which was significantly inhibited by both saturated and unsaturated fatty acids. Our data demonstrate that functional association of β1-subunit with hH1αmodifies the kinetics and fatty acid block of the Na+channel.