Modulation of pacemaker activity in sheep cardiac Purkinje fibers by stimulation of beta-adrenoceptor subtypes.

The electrophysiological effects mediated by beta 1- and beta 2-adrenoceptors in spontaneously active sheep cardiac Purkinje fibers were investigated using the non-selective agonist (-)-isoproterenol (IPN) and the selective agonists (-)-noradrenaline (beta 1) and procaterol (beta 2) in the absence and presence of the selective antagonists bisoprolol (beta 1) and ICI 118,551 (beta 2). IPN (0.01 mumol/l) increased the spontaneous rate by 54% and the slope of diastolic depolarization by 68% of the respective control values. Further, IPN increased the action potential duration at -20 mV (APD -20 mV) from 96 to 154 ms, reduced the APD-70 mV by 17% and the duration of the diastole by 39% and slightly hyperpolarized the maximum diastolic potential. These effects were partially inhibited by ICI 118,551 (0.03 mumol/l), diminished by bisoprolol (0.1 mumol/l) and almost completely blocked by the combination of both antagonists. Concentration response curves of IPN were influenced by the selective antagonists as follows: ICI 118,551 (0.03 mumol/l) shifted the curves to the right by 0.2-0.4 log units and increased the slope factor. Bisoprolol (0.1 mumol/l) induced a greater shift to the right by 1.1-1.5 log units. Combination of bisoprolol with ICI 118,551 shifted the curves to the right by 1.5-1.7 log units. Noradrenaline (0.3 mumol/l) elicited similar actions as IPN. Bisoprolol (0.1 mumol/l) shifted the concentration response curves of noradrenaline to the right by 1.1-1.9 log units. Actions of procaterol (0.1 mumol/l) were weak, attained only 15-35% of the maximal effects of IPN and could be blocked by ICI 118,551 (0.03 mumol/l). These results show that the increase of pacemaker activity induced by catecholamines in sheep cardiac Purkinje fibers is predominantly mediated by stimulation of beta 1-receptors. However, contribution of beta 2-receptor mediated effects could be demonstrated.