The Journal of Physiological Sciences
Online ISSN : 1880-6562
Print ISSN : 1880-6546
Regular Papers
Modeling the Calcium Gate of Cardiac Gap Junction Channel
Chiaki OkaHiroyuki MatsudaNobuaki SaraiAkinori Noma
Author information
JOURNALS FREE ACCESS

2006 Volume 56 Issue 1 Pages 79-85

Details
Abstract

We addressed the question how Ca2+ transients affect gap junction conductance (Gj) during action potential (AP) propagation by constructing a dynamic gap junction model coupled with a cardiac cell model. The kinetics of the Ca2+ gate was determined based on published experimental findings that the Hill coefficient for the [Ca2+]iGj relationship ranges from 3 to 4, indicating multiple ion bindings. It is also suggested that the closure of the Ca2+ gate follows a single exponential time course. After adjusting the model parameters, a two-state (open-closed) model, assuming simultaneous ion bindings, well described both the single exponential decay and the [Ca2+]iGj relationship. Using this gap junction model, 30 cardiac cell models were electrically connected in a one-dimensional cable. However, Gj decreased in a cumulative manner by the repetitive Ca2+ transients, and a conduction block was observed. We found that a reopening of the Ca2+ gate is possible only by assuming a sequential ion binding with one rate limiting step in a multistate model. In this model, the gating time constant (τ) has a bell-shaped dependence on [Ca2+]i, with a peak around the half-maximal concentration of [Ca2+]i. Here we propose a five-state model including four open states and one closed state, which allows normal AP propagation; namely, the Gj is decreased ∼15% by a single Ca2+ transient, but well recovers to the control level during diastole. Under the Ca2+-overload condition, however, the conduction velocity is indeed decreased as demonstrated experimentally. This new gap junction model may also be useful in simulations of the ventricular arrhythmia.

Information related to the author
© 2006 by The Physiological Society of Japan
Previous article Next article
feedback
Top