Effects of noradrenaline on the sodium pump of guinea pig ventricle.
The effect of noradrenaline on myocardial sodium-pump activity has been studied, using a direct measure of active ion transport via the pump; namely, the ouabain-sensitive uptake of the radioisotope and potassium analogue rubidium-86 into guinea pig ventricular tissue slices. Physiological concentrations of noradrenaline caused a dose-dependent stimulation of rubidium uptake (peak response at 2 X 10(-7) M). With higher concentrations, the uptake fell progressively. At 6 X 10(-5) M, noradrenaline uptake was lower than control. The stimulatory action is not mediated by classic adrenergic mechanisms. It was not blocked by either alpha- or beta-blockade. Indirect actions via changes in membrane permeability to sodium and potassium ions are also considered. The inhibitory effect of high concentrations of noradrenaline, however, was mediated by alpha-receptors. Stimulation of the pump by noradrenaline could stabilize cellular ion concentrations and resting membrane potential. Since the pump is electrogenic, this is one mechanism by which noradrenaline will cause shortening of action potential. This may provide an explanation for the greater Q-T shortening during exercised-induced tachycardia, compared with atrial pacing. At high concentrations, attained locally during maximal sympathetic stimulation, these advantageous effects may be lost.
Wanless
R B
RB
Noble
M I
MI
Drake-Holland
A J
AJ
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D007473:Ion Channels; D011941:Receptors, Adrenergic; D012964:Sodium; D011433:Propranolol; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D009638:Norepinephrine; D010646:Phentolamine