Effects of buffer magnesium on positive inotropic agents in guinea pig cardiac muscle

Experiments examined effects of extracellular Mg2+ concentration (Mgo2+) on dose-dependent actions of strophanthidin, norepinephrine, Bay K-8644 and extracellular Ca2+ (Cao2+) in electrically stimulated atrial and ventricular muscle isolated from guinea pig heart. Mgo2+ itself elicited a concentration-dependent negative inotropic effect. Elevation of Mgo2+ between 0.6 and 12 mM increased the concentration of strophanthidin necessary to produce its toxic effects without affecting the maximum developed tension prior to toxicity. Similarly, Mgo2+ did not alter the maximum contractile force elicited by cumulative addition of norepinephrine, Bay K-8644 or Cao2+, but increased their ED50 values. These data suggest that interactions between Mgo2+ and the four positive inotropic agents were not mediated by effects on receptor binding or Na+,K+-ATPase, but rather by alterations at one or more steps involved in excitation-contraction coupling.