Analysis of the hyperpolarizing effect of catecholamines on canine cardiac Purkinje fibres

The hyperpolarization induced by catecholamines on barium-depolarized (0.2-0.8 mM BaCl) canine cardiac Purkinje fibres, in vitro, was studied by use of conventional microelectrode recordings of transmembrane electrical potentials. 2. Noradrenaline, adrenaline and isoprenaline hyperpolarized Purkinje fibres in a concentration-dependent manner from a threshold concentration around 5 nM. The three catecholamines were shown to be approximately equipotent. Tachyphylaxis was observed when the interval between catecholamine applications was less than 15 min. 3. Atenolol (10 microM) blocked the hyperpolarization reversibly and theophylline (0.5 mM) potentiated it. 4. Tetrodotoxin (5 microM) did not affect the hyperpolarization induced by isoprenaline. Acetylcholine and histamine, up to 10 microM, were not effective in hyperpolarizing Purkinje fibres. 5. Low extracellular potassium concentrations (zero and 1 mM) did not affect the hyperpolarization, but high extracellular potassium concentrations (10-20 mM), markedly reduced the effect of isoprenaline (100 nM). 6. Reduction of the extracellular sodium concentration produced a roughly proportional reduction in the isoprenaline-induced hyperpolarization. The hyperpolarization was reversibly blocked in 34 mM sodium Tris-Tyrode solution. 7. The hyperpolarization was not reduced in Tyrode solution containing 0.6 mM calcium, but was drastically reduced in zero-calcium Tyrode solution. This effect was reversible. 8. Addition of verapamil (5-10 microM) diminished the hyperpolarization, in a concentration-dependent manner. This effect was partially reversed after washing. 9. Ouabain (0.7-1 microM) significantly reduced the isoprenaline-induced hyperpolarization, but 2,4-dinitrophenol (0.2 mM) did not affect it. 10. Caesium chloride (20 mM) abolished the hyperpolarization. The blockade was only partially reversed upon washing. 11. It is suggested that the hyperpolarization induced by a short exposure to catecholamines is mainly due to an increase in potassium permeability (PK). A mechanism involving calciumdependent potassium channels might underlie the increase in PK.