Alpha adrenoceptor stimulation reduces outward currents in rat ventricular myocytes.
The effects of alpha adrenoceptor stimulation with noradrenaline were investigated in rat ventricular myocytes after blockade of beta receptors with propranolol (1 microM). At room temperature and low stimulation frequency (0.5 Hz), noradrenaline evoked a phentolamine-sensitive increase in contraction amplitude by 22%. The action potentials of myocytes were prolonged. When the sodium current was inactivated by depolarization in whole-cell voltage clamp experiments, noradrenaline caused a small, but highly variable increase in net inward current and shifted the current-voltage relation between -30 and -5 mV to the hyperpolarizing direction. These effects were absent when K+ currents were inhibited by Cs+ substitution. After inhibition of the Ca++ current with Cd++ (0.1 mM), noradrenaline decreased the peak transient outward current; it reduced the steady-state outward current in a concentration-dependent manner (pD2 value, 6.9), but had no effect on the amplitude of the transient component of outward current. Noradrenaline reduced holding current at -40 mV. The inward branch of the inward rectifier was not affected. The noradrenaline-induced changes in membrane currents were significantly smaller in the presence of phentolamine (10 microM). They are therefore considered to be mediated by alpha adrenoceptor stimulation. The reduction in outward currents can explain the prolongation in action potential duration which could contribute to the increase in contractility.
Ravens
U
U
Department of Pharmacology, University of Essen, W. Germany.
Wang
X L
XL
Wettwer
E
E
D000818:Animals; D002478:Cells, Cultured; D004553:Electric Conductivity; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D016276:Ventricular Function
D011942:Receptors, Adrenergic, alpha; D011433:Propranolol; D009638:Norepinephrine; D010646:Phentolamine