Modulation of cardiac Na+ channel expression in Xenopus oocytes by beta 1 subunits.
Voltage-gated Na+ channels consist of a large alpha subunit of 260 kDa associated with beta 1 and/or beta 2 subunits of 36 and 33 kDa, respectively. alpha subunits of rat cardiac Na+ channels (rH1) are functional when expressed alone in Xenopus oocytes or mammalian cells. beta 1 subunits are present in the heart, and localization of beta 1 subunit mRNA by in situ hybridization shows expression in the perinuclear cytoplasm of cardiac myocytes. Coexpression of beta 1 subunits with rH1 alpha subunits in Xenopus oocytes increases Na+ currents up to 6-fold in a concentration-dependent manner. However, no effects of beta 1 subunit coexpression on the kinetics or voltage dependence of the rH1 Na+ current were detected. Increased expression of Na+ currents is not observed when an equivalent mRNA encoding a nonfunctional mutant beta 1 subunit is coexpressed. Our results show that beta 1 subunits are expressed in cardiac muscle cells and that they interact with alpha subunits to increase the expression of cardiac Na+ channels in Xenopus oocytes, suggesting that beta 1 subunits are important determinants of the level of excitability of cardiac myocytes in vivo.
Qu
Y
Y
Department of Pharmacology, University of Washington, Seattle 98195-7280, USA.
Isom
L L
LL
Westenbroek
R E
RE
Rogers
J C
JC
Tanada
T N
TN
McCormick
K A
KA
Scheuer
T
T
Catterall
W A
WA
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000648:ultrastructure; D004553:Electric Conductivity; D005260:Female; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D009865:Oocytes; D018408:Patch-Clamp Techniques; D011487:Protein Conformation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014981:Xenopus
D012333:RNA, Messenger; D011994:Recombinant Proteins; D015222:Sodium Channels; D012964:Sodium