The mechanism of Ca2+ action on the healing-over process in mammalian cardiac muscles: a kinetic analysis.

The effect of Ca2+ concentration and temperature on the recovery of membrane potential after investigating lesions using sucrose-gap technique in the guinea-pig papillary muscles were studied. At certain temperatures, this recovery showed increased accerelation with increasing Ca2+ concentration. The relation between rate constant of the recovery and Ca2+ concentration was quite similar to that of the reaction between an enzyme and substrate. This relationship could be expressed by the equation Y = xn(Km + xn), where Y is the normalized rate constant and x the Ca2+ concentration. The coefficient, n, was evaluated by performing Hill's plot. The value of n largely changed between 1 and ca. 2 at 32 degrees C--37 degrees C. The input resistance fell at the instant of formation of a lesion and started to rise with recovery of membrane potential. The resistance change after lesion formation was also observed in the potassium-Tyrode's solution in which Na+ was substituted with K+. The concentration-rate relationship of Ca2+ in the healing-over seems to indicate that Ca2+ binds to some molecules in the junctional membrane and produce a structural change of intercalated disc which brings about the healing-over. The large change of n suggests that Ca2+ has a cooperative action in the healing-over process, or alternatively that the state of membrane lipids has some effect on the process.