The intracellular domain of the beta 2 subunit modulates the gating of cardiac Na v 1.5 channels.
We have previously shown that the transmembrane segment plus either the extracellular or intracellular domain of the beta1 subunit are required to modify cardiac Na(v)1.5 channels. In this study, we coexpressed the intracellular domain of the beta2 subunit in a beta1/beta2 chimera with Na(v)1.5 channels in Xenopus oocytes and obtained an atypical recovery behavior of Na(v)1.5 channels not reported before for other Na(+) channels: Recovery times of up to 20 ms at -120 mV produced a similar fast recovery as observed for Na(v)1.5/beta1 channels, but the current amplitude decreased again at longer recovery times and reached a steady-state level after 1-2 s with current amplitudes of only 43 +/- 2% of the value at 20 ms. Current reduction was accompanied by slowed inactivation and by a shift of steady-state activation toward depolarized potentials by 9 mV. All effects were reversible and they were not seen when deleting the beta2 intracellular domain. These results describe the first functional effects of a beta2 subunit region on Na(v)1.5 channels and suggest a novel closed state in cardiac Na(+) channels accessible at hyperpolarized potentials.
Zimmer
Thomas
T
Institute of Physiology II, Friedrich Schiller University, Jena, Germany. thomas.zimmer@mti.uni-jena.de
Benndorf
Klaus
K
D000818:Animals; D006801:Humans; D009124:Muscle Proteins / Q000737:chemistry* / Q000502:physiology*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry* / Q000502:physiology*; D051381:Rats; D015222:Sodium Channels / Q000737:chemistry* / Q000502:physiology*
D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D021122:Protein Subunits; C568320:SCN5A protein, human; C568322:Scn5a protein, rat; D015222:Sodium Channels