Magnesium gating of cardiac gap junction channels

We aimed to study kinetics of modulation by intracellular Mg2+ of cardiac gap junction (Mg2+ gate). Paired myocytes of guinea-pig ventricle were superfused with solutions containing various concentrations of Mg2+. In order to rapidly apply Mg2+ to one aspect of the gap junction, the non-junctional membrane of one of the pair was perforated at nearly the connecting site by pulses of nitrogen laser beam. The gap junction conductance (Gj) was measured by clamping the membrane potential of the other cell using two-electrode voltage clamp method. The laser perforation immediately increased Gj, followed by slow Gj change with time constant of 3.5 s at 10 mM Mg2+. Mg2+ more than 1.0 mM attenuated dose-dependently the gap junction conductance and lower Mg2+ (0.6 mM) increased Gj with a Hill coefficient of 3.4 and a half-maximum effective concentration of 0.6 mM. The time course of Gj changes was fitted by single exponential function, and the relationship between the reciprocal of time constant and Mg2+ concentration was almost linear. Based on the experimental data, a mathematical model of Mg2+ gate with one open state and three closed states well reproduced experimental results. One-dimensional cable model of thirty ventricular myocytes connected to the Mg2+ gate model suggested a pivotal role of the Mg2+ gate of gap junction under pathological conditions.