title: Functional association of the beta 1 subunit with human cardiac (hH1) and rat skeletal muscle (mu 1) sodium channel alpha subunits expressed in Xenopus oocytes.
abstract: Native cardiac and skeletal muscle Na channels are complexes of alpha and beta 1 subunits. While structural correlates for activation, inactivation, and permeation have been identified in the alpha subunit and the expression of alpha alone produces functional channels, beta 1-deficient rat skeletal muscle (mu 1) and brain Na channels expressed in Xenopus oocytes do not gate normally. In contrast, the requirement of a beta 1 subunit for normal function of Na channels cloned from rat heart or human heart (hH1) has been disputed. Coinjection of rat brain beta 1 subunit cRNA with hH1 (or mu 1) alpha subunit cRNA into oocytes increased peak Na currents recorded 2 d after injection by 240% (225%) without altering the voltage dependence of activation. In mu 1 channels, steady state inactivation was shifted to more negative potentials (by 6 mV, p < 0.01), but the shift of 2 mV was not significant for hH1 channels. Nevertheless, coexpression with beta 1 subunit speeded the decay of macroscopic current of both isoforms. Ensemble average hH1 currents from cell-attached patches revealed that coexpression of beta 1 increases the rate of inactivation (quantified by time to 75% decay of current; p < 0.01 at -30, -40, and -50 mV). Use-dependent decay of hH1 Na current during repeated pulsing to -20 mV (1 s, 0.5 Hz) after a long rest was reduced to 16 +/- 2% of the first pulse current in oocytes coexpressing alpha and beta 1 subunits compared to 35 +/- 8% use-dependent decay for oocytes expressing the alpha subunit alone. Recovery from inactivation of mu 1 and hH1 Na currents after 1-s pulses to -20 mV is multiexponential with three time constants; coexpression of beta 1 subunit decreased all three recovery time constants. We conclude that the beta 1 subunit importantly influences the function of Na channels produced by coexpression with either the hH1 or mu 1 alpha subunits.
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: H B
authors.initials: HB
authors.lastname: Nuss
authors.forename: N
authors.initials: N
authors.lastname: Chiamvimonvat
authors.forename: M T
authors.initials: MT
authors.lastname: Pérez-García
authors.forename: G F
authors.initials: GF
authors.lastname: Tomaselli
authors.forename: E
authors.initials: E
authors.lastname: Marbán
mesh_terms: D000818:Animals; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006321:Heart / Q000502:physiology*; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D009865:Oocytes; D051381:Rats; D015222:Sodium Channels / Q000502:physiology*; D013997:Time Factors
chemical_list: D015222:Sodium Channels