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.
Article|
December 01 1995
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.
H B Nuss,
H B Nuss
Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
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N Chiamvimonvat,
N Chiamvimonvat
Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
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M T Pérez-García,
M T Pérez-García
Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
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G F Tomaselli,
G F Tomaselli
Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
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E Marbán
E Marbán
Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
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H B Nuss
Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
N Chiamvimonvat
Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
M T Pérez-García
Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
G F Tomaselli
Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
E Marbán
Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Online ISSN: 1540-7748
Print ISSN: 0022-1295
J Gen Physiol (1995) 106 (6): 1171–1191.
Citation
H B Nuss, N Chiamvimonvat, M T Pérez-García, G F Tomaselli, E Marbán; 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.. J Gen Physiol 1 December 1995; 106 (6): 1171–1191. doi: https://doi.org/10.1085/jgp.106.6.1171
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