Abstract:
: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.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Kurata Y,Sato R,Hisatome I,Imanishi Sdoi
10.1016/S0006-3495(99)77031-1subject
Has Abstractpub_date
1999-10-01 00:00:00pages
1885-904issue
4eissn
0006-3495issn
1542-0086pii
S0006-3495(99)77031-1journal_volume
77pub_type
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