Differential potentiation by depolarization of the effects of @entity460 antagonists on contraction and @entity141 current in XXXX heart.

@entity1855 @entity840 @entity3988 @entity460 @entity594 @entity141
1. The effects of elevation of extracellular K+ concentration ([K+]o) on the negative inotropic potencies of three representative @entity460 antagonists, @entity3988 , @entity1855 and @entity594 , were investigated in @entity840 papillary muscle preparations. 2. The negative inotropic effect of @entity3988 was potentiated 110 fold when [K+]o was raised from 2.7 mM to 12.7 mM. The effect of @entity1855 was also potentiated to a lesser extent, but that of @entity594 was not affected. 3. Resting membrane potentials in ventricular muscles were about -80 mV and -60 mV in 2.7 mM K+ and 12.7 mM K+, respectively. 4. To clarify the mechanism responsible for the differential potentiation of the negative inotropic effects, the blocking actions of the three @entity460 antagonists on the L-type @entity141 channel current (ICa(L)) were compared at the holding potentials of -80 mV and -60 mV by the whole-cell patch-clamp technique. 5. The use-dependent blocking effect of @entity3988 on ICa(L) was enhanced markedly by the change in the holding potential from -80 mV to -60 mV. The effect of @entity1855 was also enhanced to a lesser extent but that of @entity594 was not affected in this range of depolarization. 6. The differential effects of the [K+]o elevation on the negative inotropic potencies of the three @entity460 antagonists are explained by the differences in voltage-dependency of their use-dependent blocking effects on ICa(L). 7. The properties of @entity3988 and @entity1855 observed in this study may contribute to their protective effects on the ischaemic myocardium, without affecting the normal myocardium.
