Analysis and modeling of na current in cardiac muscles

心筋Na電流の解析とそのモデル化

Analysis and modeling of na current in cardiac muscles

Creators Sada Hideaki

Creators Tanaka Kotaro

Creators Ebina Yoshio

Creators Ban Takashi

The (Na)^+ channel plays essential roles in initiation and conduction of action potential in a variety of excitable tissues including nerves, hearts and muscles. Na channels undergo activation and inactivation depending on the membrane voltage and time. Hodgkin & Huxley (H-H), early in 1950s, proposed a mathematical model to describe Na channel properties of the squid axonal membrane, based on voltage-clamp (V-C) study. For the next 3 decades since then, direct recording of the Na current by V-C method and hence the study of Na channel property have been hampered in cardiac tissues largely by the complicated geometry of the tissue. Recent electrophysiological studies using V-C method with patch-pipettes on dispersed single heart cells have demonstrated that the gating-kinetics of Na channels is much more complicated than predicted from the H-H model. To establish a new model which enables describing Na channel events in heart, we conducted V-C study in embryonic chick heart cells. In this preparation, we found pronounced differences in the inactivation and re-inactivation mechanisms from those in the axon, suggesting a presence of one conductive and two inactivated states among which voltage-dependent transitions were permitted (a cyclic reaction model). According to the model, we experimentally determined rate-constants of the reaction. We also found a delay in onset of inactivation as well as activation in voltage-clamped heart cells, and derived empirical equations for such delays in onset. Taken above together, we could faithfully reproduce the Na channel currents observed in heart cells under V-C conditions.

[ISSN]0372-7661

[NCID]AN00244228