Noradrenaline hyperpolarizes cells of the canine coronary sinus by increasing their permeability to potassium ions.

Abstract

SUMMARY1. The mechanism ofthe noradrenaline-induced hyperpolarization was investigated in small strips of coronary sinus tissue mounted in a fast-flow system.2. The recorded hyperpolarization was negligibly small in response to 10 nmnoradrenaline but was maximal at 10/SM (average amplitude 23 mV, in 4 mM-K solution). The hyperpolarization was unaffected by 1 /SM-phentolamine but was abolished by 10 /uM-propranolol and so is presumably mediated via fl-adrenoceptors.3. The noradrenaline-induced hyperpolarization became smaller when the extracellular K concentration ([K]0) was raised or when the extracellular Na concentration was lowered.4. 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).5. The noradrenaline-induced hyperpolarization is not diminished during exposure to 5 ,uM-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. 6. 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.7. The cross-over or 'reversal' potentials of current-voltage curves, determined with and without the drugs, vary with [K]0 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.

.BETA.-Actions of catecholamines on the K-related currents of the bullfrog atrial muscle.

“…The hyperpolarization induced by j3-agonists was attributed to an enhancement of Na-K pump activity (TRAUTWEIN and SCHMIDT, 1960;AKASU et al, 1977). But, BOYDEN et al (1983) noted direct action of j3-agonists on permeability of potassium in the canine coronary sinus, and GADSBY (1983) reported similar findings in the case of Purkinje fibers. j3-Agonists are also considered to enhance the outward current (lout) through an increase in the slow inward current (Isi) in view of the Ca activated outward current (SIEGELBAUM et a1.,1977;SIEGELBAUM and TSIEN, 1980;GoTo et al, 1982GoTo et al, , 1983URATA and GoTo, 1982).…”

“…From these results it was proposed that /3-agonists directly increase the background 'k, currents. Recently, BOYDEN et al (1983) andGADSBY (1983) noted that hyperpolarization was a direct action induced by ,9-agonists, something which has usually been attributed to the enhancement of the Na pump activity. They observed that R-agonists could induce a hyperpolarization in the canine coronary sinus and Purkinje fibers even after the inhibition of Na pump by acetylstrophanthidin and/ or K-free solution and that the reversal potentials of I V curves determined with and without the drugs vary with [K]0 as does Ek, and concluded that j3-agonists increased the K permeability directly, as did the cholinergic agonists.…”

The basis for the membrane potential of quiescent cells of the canine coronary sinus.

“…This was verified in some experiments by application of ACh in the presence of low [Na]0, which resulted in a further hyperpolarization of a few millivolts (see Fig. 5B of Boyden et al 1983). It seems likely that at least some of the remaining deviation of the membrane potential from EK in low Na solution can be attributed to inward current carried by the remaining extracellular Na ions.…”

“…sudden application of acetylcholine, sudden increase in [K]0, or sudden decrease in [Na]0, the resting potential attains within a few seconds a level that indicates that EK and [K]i are high. In fact, the 176 P. A. BOYDEN, P. F. CRANEFIELD, D. C. GADSBY AND A. L. WIT membrane potentials attained during those interventions indicate that [K]i is normally about 155 mm in coronary sinus cells (see also Boyden et al 1983), a value similar to that reported for Purkinje fibres (Carmeliet, 1961;Miura, Rosen & Hoffman, 1977;Gadsby & Cranefield, 1977;Wier, 1978;Sheu, Korth, Lathrop & Fozzard, 1980;Wiederholt, Daniesevskis, Hansen, Lickey & Platsch, 1980), for myocardial cells of ventricles (Lee & Fozzard, 1975;Cohen & Fozzard, 1978;Browning & Strauss, 1981;Baumgarten, Cohen & McDonald, 1981) and atria (Singer, Baumgarten & Miller, 1980;Browning, Kerr & Strauss, 1980) and for cells of the sino-atrial node (Browning et al 1980) and atrio-ventricular node (Baumgarten, 1982). Since the resting potential normally lies so far from EK, the cell membrane clearly cannot be exclusively permeable to K ions.…”

“…However, a marked hyperpolarization can be evoked in such cells by application of acetylcholine or noradrenaline (Wit & Cranefield, 1977;Wit, Cranefield & Gadsby, 1980; cf. Boyden, Cranefield & Gadsby 1983). It is necessary to understand the basis ofthe resting potential of coronary sinus cells before attempting to explain either the effects of noradrenaline or the complex changes in the resting, or maximum diastolic, potential that are seen after, and during, bursts of triggered activity under a variety of conditions (Wit & Cranefield, 1977;Gadsby, Wit & Cranefield, 1979;Wit, Cranefield & Gadsby, 1980.…”