Mechanisms of cation permeation in cardiac sodium channel: description by dynamic pore model.
The selective permeability to monovalent metal cations, as well as the relationship between cation permeation and gating kinetics, was investigated for native tetrodotoxin-insensitive Na-channels in guinea pig ventricular myocytes using the whole-cell patch clamp technique. By the measurement of inward unidirectional currents and biionic reversal potentials, we demonstrate that the cardiac Na-channel is substantially permeable to all of the group Ia and IIIa cations tested, with the selectivity sequence Na(+) >/= Li(+) > Tl(+) > K(+) > Rb(+) > Cs(+). Current kinetics was little affected by the permeant cation species and concentrations tested (</=160 mM), suggesting that the permeation process is independent of the gating process in the Na-channel. The permeability ratios determined from biionic reversal potentials were concentration and orientation dependent: the selectivity to Na(+) increased with increasing internal [K(+)] or external [Tl(+)]. The dynamic pore model describing the conformational transition of the Na-channel pore between different selectivity states could account for all the experimental data, whereas conventional static pore models failed to fit the concentration-dependent permeability ratio data. We conclude that the dynamic pore mechanism, independent of the gating machinery, may play an important physiological role in regulating the selective permeability of native Na-channels.
Kurata
Y
Y
Department of Physiology, Kanazawa Medical University, Ishikawa 920-0293, Japan.
Sato
R
R
Hisatome
I
I
Imanishi
S
S
D000818:Animals; D002414:Cations, Monovalent / Q000378:metabolism* / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D006168:Guinea Pigs; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008670:Metals / Q000378:metabolism / Q000494:pharmacology; D008954:Models, Biological; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000378:metabolism*; D055672:Static Electricity; D013779:Tetrodotoxin / Q000494:pharmacology
D002414:Cations, Monovalent; D008670:Metals; D015222:Sodium Channels; D013779:Tetrodotoxin