COEXPRESSION OF BETA-1 WITH CARDIAC SODIUM-CHANNEL ALPHA-SUBUNITS IN OOCYTES DECREASES LIDOCAINE BLOCK

Coexpression of the rat beta 1 subunit with rat brain and skeletal mus cle sodium channel a subunits in Xenopus oocytes normalizes currents b y accelerating sodium current decay kinetics, shifting steady state av ailability relationships, and accelerating recovery from inactivation. Unlike brain and skeletal muscle, the heart a subunit expressed witho ut beta 1 has native-like decay kinetics in oocytes. Messenger RNA for beta 1 has been found in heart, but whether and how it affects cardia c sodium channel function are unclear. We studied coexpression of huma n heart a subunit with beta 1 in Xenopus oocytes using two microelectr ode voltage-clamp and macropatch techniques. Coexpression with beta 1 caused a significant positive shift of 3 - 7 mV in the midpoint of the steady state inactivation relationship but did not affect single-chan nel conductance, activation, current decay, or recovery from inactivat ion. Sensitivity to lidocaine block, however, was decreased for both r esting state block (K-d = 0.5 - 1.3 mM) and phasic block in response t o pulse trains, but inactivated state block was not affected (K-d = si milar to 10 mu M). Coexpression with beta 1 increased the rate of reco very from;lidocaine block, which accounted for the major part of the o bserved differences in tonic and phasic block. A beta 1 construct with the cytoplasmic tail removed also produced these effects, demonstrati ng that the beta 1 cytoplasmic tail was not involved in altering lidoc aine block. We conclude that the beta 1 subunit is capable of affectin g function of the cardiac sodium channel in oocytes by decreasing toni c and phasic lidocaine block with small effects on gating.