Noradrenaline hyperpolarizes cells of the canine coronary sinus by increasing their permeability to potassium ions.
The mechanism of the noradrenaline-induced hyperpolarization was investigated in small strips of coronary sinus tissue mounted in a fast-flow system. The recorded hyperpolarization was negligibly small in response to 10 nM-noradrenaline but was maximal at 10 microM (average amplitude 23 mV, in 4 mM-K solution). The hyperpolarization was unaffected by 1 microM-phentolamine but was abolished by 10 microM-propranolol and so is presumably mediated via beta-adrenoceptors. The noradrenaline-induced hyperpolarization became smaller when the extracellular K concentration ([K]o) was raised or when the extracellular Na concentration was lowered. These results are consistent with two general mechanisms: noradrenaline might cause hyperpolarization by stimulating the Na/K pump to generate more outward current, as previously suggested for other cell types. Alternatively, noradrenaline might lower the permeability ratio, PNa/PK, by reducing the permeability coefficient for Na (PNa) and/or increasing that for K (PK). The noradrenaline-induced hyperpolarization is not diminished during exposure to 5 microM-acetylstrophanthidin, or to K-free solution, or to K-free solution containing acetylstrophanthidin. We conclude that the hyperpolarization does not reflect enhanced electrogenic pump activity. Conductance measurements using two micro-electrodes in very small preparations revealed that, like the muscarinic agonist carbachol, noradrenaline caused an increase in membrane slope conductance. Steady-state current-voltage curves obtained in the presence of noradrenaline, in the presence of carbachol, and in the absence of both drugs all crossed each other at about the same level of membrane potential. During the maintained injection of sufficiently large hyperpolarizing current, application of either noradrenaline or carbachol causes depolarization instead of hyperpolarization. The cross-over or 'reversal' potentials of current-voltage curves, determined with and without the drugs, vary with [K]o approximately as does the K equilibrium potential calculated assuming the intracellular K concentration to be 155 mM. We conclude that, like carbachol and acetylcholine, noradrenaline causes a specific increase in the K permeability of coronary sinus cells.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D003331:Coronary Vessels / Q000378:metabolism / Q000502:physiology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology; D013327:Strophanthidin / Q000031:analogs & derivatives / Q000494:pharmacology
D013327:Strophanthidin; D002217:Carbachol; D012964:Sodium; D011433:Propranolol; C004681:acetylstrophanthidin; D011188:Potassium; D009638:Norepinephrine; D010646:Phentolamine