title: Gating of skeletal and cardiac muscle sodium channels in mammalian cells.
abstract: 1. Sodium channel ionic current (INa) and gating current (Ig) were compared for rat skeletal (rSkM1) and human heart Na+ channels (hH1a) heterologously expressed in cultured mammalian cells at approximately 13 C before and after modification by site-3 toxins (Anthopleurin A and Anthopleurin B). 2. For hH1a Na+ channels there was a concordance between the half-points (V ) of the peak conductance-voltage (G-V) relationship and the gating charge-voltage (Q-V) relationship with no significant difference in half-points. In contrast, the half-point of the Q-V relationship for rSkM1 Na+ channels was shifted to more negative potentials compared with its G-V relationship with a significant difference in the half-points of -8 mV. 3. Site-3 toxins slowed the decay of INa in response to step depolarizations for both rSkM1 and hH1a Na+ channels. The half-point of the G-V relationship in rSkM1 Na+ channels was shifted by -8.0 mV while toxin modification of hH1a Na+ channels produced a smaller hyperpolarizing shift of the V by -3.7 mV. 4. Site-3 toxins reduced maximal gating charge (Qmax ) by 33% in rSkM1 and by 31% in hH1a, but produced only minor changes in the half-points and slope factors of their Q-V relationships. In contrast to measurements in control solutions, after modification by site-3 toxin the half-points of the G-V and the Q-V relationships for rSkM1 Na+ channels demonstrated a concordance similar to that for hH1a. 5. Qmax vs. Gmax for rSkM1 and hH1a Na+ channels exhibited linear relationships with almost identical slopes, as would be expected if the number of electronic charges (e-) per channel was comparable. 6. We conclude that the faster kinetics in rSkM1 channels compared with hH1a channels may arise from inherently faster rate transitions in skeletal muscle Na+ channels, and not from major differences in the voltage dependence of the channel transitions.
authors.affiliation: The Nora Eccles Harrison Cardiovascular Research & Training Institute and Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112, USA. michael@cvrti.uath.edu
authors.forename: M F
authors.initials: MF
authors.lastname: Sheets
authors.forename: D A
authors.initials: DA
authors.lastname: Hanck
mesh_terms: D000818:Animals; D002460:Cell Line; D006321:Heart / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008322:Mammals; D008564:Membrane Potentials / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D010210:Papillary Muscles / Q000502:physiology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015222:Sodium Channels / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D014162:Transfection
chemical_list: D000644:Quaternary Ammonium Compounds; D011993:Recombinant Fusion Proteins; D015222:Sodium Channels; C027917:tetramethylammonium