Paradoxical positive inotropic effect of K+ in the rat heart.
In cardiac muscle isolated from most mammalian species, an elevation of extracellular K+ concentration decreases developed tension. This is explained from stimulation of the Na pump. In rat myocardium, however, developed tension increased when K+ concentration was raised from 3.5 to 9.5 mM, seemingly inconsistent with the above explanation. Activation of isolated Na+,K+-adenosinetriphosphatase by K+ was not different in rat and guinea pig heart. The K+-induced increase in developed tension observed in left atrial muscle preparations obtained from rat heart was not blocked by phentolamine and propranolol or by reserpine pretreatment but attenuated by stimulation at higher frequency, incubation at a lower temperature, or by veratridine, all of which have been shown to increase Na+ loading of myocardial cells. K+ slightly prolonged action potential duration and partially depolarized resting membrane potential; however, K+-induced changes in electrophysiological parameters or possible inactivation of early outward current observed in myocytes isolated from rat heart are unlikely to be the primary cause of the positive inotropic effect. Caffeine or Cd2+ eliminated the inotropic effect of K+ but ryanodine was ineffective. An increase in extracellular K+ from 1 to 3.5 mM decreased developed tension. These results indicate that K+ has dual effects on developed tension in rat myocardium: a negative inotropic effect resulting from Na pump stimulation and a positive inotropic effect. The latter effect is due to a process that is either unique or more strongly expressed in the rat myocardium and masks the former effect in the range of physiological K+ concentrations.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000201:enzymology; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013696:Temperature
D007473:Ion Channels; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D002118:Calcium