In-vivo quantification of myocardial Na-K pump rate during beta-adrenergic stimulation of intact pig hearts.
Maintenance of adequate electrical activity of the heart depends critically on the ability of the Na-K pump to compensate for normal passive sodium and potassium fluxes. Using sudden injections of [3H]ouabain into the left coronary artery in anaesthetized open-chest pigs, we monitored transient changes in myocardial potassium balance by PVC-valinomycin mini-electrodes. When related to the number of pumps blocked and fractional inhibition, these data provided estimates of total Na-K pump capacity as well as actual pump rate and perturbations of the Na-K balance. Experiments were performed in hearts with and without intracoronary isoprenaline infusion (2.5 nmol min-1). After injection of 120 nmol [3H]ouabain into the left coronary artery, myocardial [3H]ouabain concentrations were 118 (74-178) and 103 (76-145) pmol g-1 and total concentrations of [3H]ouabain binding sites were 893 (752-1076) and 785 (691-877) pmol g-1 (median, 95% confidence interval) in isoprenaline-treated and control hearts respectively (differences not significant). The [3H]ouabain injection caused a net potassium release of 81 (56-132) and 43 (23-75) mumol 100 g-1 (median, 95% confidence interval) in isoprenaline-treated and control hearts respectively (n = 6-8; significance of difference, P = 0.03). Na-K pump rate estimated from mono-exponential release curves was 6363 (3942-10,858) K+ ions min-1 site-1 during beta-adrenoceptor stimulation and 2514 (1380-4322) in control (significance of difference, P = 0.03). This corresponds to 40 and 16%, respectively, of the maximum possible pump rate determined from ATP hydrolysis. Comparison of accumulated potassium release and relative Na-K pump rate indicates that catecholamines enhance the sensitivity of the Na-K pump for intracellular sodium.
Ellingsen
O
O
Institute for Experimental Medical Research, University of Oslo, Norway.
Sejersted
O M
OM
Vengen
O A
OA
Ilebekk
A
A
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000818:Animals; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007269:Injections, Intra-Arterial; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000008:administration & dosage*; D011188:Potassium / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine
D000318:Adrenergic beta-Agonists; D011955:Receptors, Drug; C028996:cardiac glycoside receptors; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium