Electrophysiological characterization of histamine receptor subtypes in sheep cardiac Purkinje fibers.

The histamine-receptor-subtype-mediated effects on action potentials of electrically driven and spontaneously active isolated sheep cardiac Purkinje fibers were investigated using H1- and H2-selective agonists and antagonists. In electrically stimulated Purkinje fibers, histamine (3 mumol/l) increased the action potential plateau height, decreased the action potential duration measured at a repolarization level of -60 mV and enhanced the pacemaker activity. These effects were abolished by the H2-selective antagonist cimetidine (30 mumol/l), but were not impaired by the H1-selective antagonist dimetindene (0.3 mumol/l). In spontaneously active Purkinje fibers, histamine (10 mumol/l) increased the spontaneous rate by 24%, the slope of diastolic depolarization by 45% and shortened the duration of the diastole by 32% of the respective control measurements. These effects were blocked by 30 mumol/l cimetidine, but remained unchanged in the presence of 0.3 mumol/l dimetindene. Concentration-response curves of histamine were shifted to the right by approximately 2 logarithmic units in the presence of 30 mumol/l cimetidine, but were not influenced in the presence of 0.3 mumol/l dimetindene. The H2-selective agonist impromidine (0.001-0.3 mumol/l) had similar actions as histamine on spontaneously active Purkinje fibers, while the H1-selective agonist 2-(2-pyridyl-)ethylamine was ineffective. It is concluded that the pronounced stimulatory action of histamine on spontaneous activity in sheep cardiac Purkinje fibers is exclusively mediated by H2 receptors.