Gating of skeletal and cardiac muscle sodium channels in mammalian cells

Citation
Mf. Sheets et Da. Hanck, Gating of skeletal and cardiac muscle sodium channels in mammalian cells, J PHYSL LON, 514(2), 1999, pp. 425-436
Citations number
28
Categorie Soggetti
Physiology
Journal title
JOURNAL OF PHYSIOLOGY-LONDON
ISSN journal
00223751 → ACNP
Volume
514
Issue
2
Year of publication
1999
Pages
425 - 436
Database
ISI
SICI code
0022-3751(19990115)514:2<425:GOSACM>2.0.ZU;2-D
Abstract
1. Sodium channel ionic current (I-Na) and gating current (I-g) were compar ed for rat skeletal (rSkM1) and human heart Na+ channels (hH1a) heterologou sly expressed in cultured mammalian cells at similar to 13 degrees 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 -1/2) of the peak conductance-voltage (G-V) relationship and the gating cha rge-voltage (Q-V) relationship with no significant difference in half-point s. In contrast, the half-point of the Q-V relationship for rSkM1. Na+ chann els was shifted to more negative potentials compared with its G-V relations hip with a significant difference in the half-points of -8 mV. 3. Site-3 toxins slowed the decay of I-Na in response to step depolarizatio ns for both rSkM1 and hH1a Na+ channels. The half-point of the G-V relation ship 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-1/2 by -3.7 mV. 4. Site-3 toxins reduced maximal gating charge (Q(max)) by 33% in rSkM1 and by 31% in hH1a, but produced only minor changes in the half-points and slo pe factors of their Q-V relationships. In contrast to measurements in contr ol 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 concordanc e similar to that for hH1a. 5. Q(max) vs. G(max) for rSkM1. and hH1a Na+ channels exhibited linear rela tionships 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 hH1 a channels may arise from inherently faster rate transitions in skeletal mu scle Na+ channels, and not from major differences in the voltage dependence of the channel transitions.