Modification of the effects of histamine and norepinephrine on the sinoatrial node pacemaker by potassium and calcium
The purpose of these experiments was to investigate the ionic bases for the effects of histamine on cardiac automaticity. Histamine and norepinephrine are known to display similar cardiac effects, and explanations for the actions of norepinephrine have been advanced. We have compared the effects of these two amines on the guinea-pig sinoatrial pacemaker at various extracellular concentrations of potassium [K+]0 and calcium [Ca++]0. Histamine increased the rate of firing of the sinoatrial node by enhancing the rate of phase 4 depolarization. An increase in [K+]0 (5.6 -13.5 mM) caused a slowing of the sinoatrial rate. This effect was antagonized by both histamine and norepinephrine in a concentration-related fashion (5 x 10-7 to 10-5 M). When [K+]0 was increased to 22 mM and spontaneously occurring potentials were abolished, histamine restored excitability of the sinoatrial preparation and initiated spontaneous activity. This effect was competitively antagonized by burimamide. Reinitiation of spontaneous activity by either histamine or norepinephrine was also observed in atrial preparations arrested by tetrodotoxin. The ability of either histamine or norepinephrine to accelerate the sinoatrial pacemaker was increased with increasing [Ca++]0 between 0 and 1.8 mM. Although the similarity of actions for histamine and norepinephrine suggests a final common pathway at the molecular level, it is probable that histamine and norepinephrine induce changes in membrane ionic conductance via two separate and pharmacologically distinct receptors.