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
Hb. Nuss et al., 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, The Journal of general physiology, 106(6), 1995, pp. 1171-1191
Native cardiac and skeletal muscle Na channels are complexes of alpha
and beta(1) subunits. While structural correlates for activation, inac
tivation, and permeation have been identified in the alpha subunit and
the expression of alpha alone produces functional channels, beta(1)-d
eficient 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 oocyt
es increased peak Na currents recorded 2 d after injection by 240% (22
5%) without altering the voltage dependence of activation. In mu 1 cha
nnels, steady state inactivation was shifted to more negative potentia
ls (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 hH
1 currents from cell-attached patches revealed that coexpression of be
ta(1) increases the rate of inactivation (quantified by time to 75% de
cay 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) aft
er 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 or subunit alone. Recov
ery 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 conclu
de that the beta(1) subunit importantly influences the function of Na
channels produced by coexpression with either the hH1 or mu 1 alpha su
bunits.