Modification of isolated atrial chronotropic histamine receptor responses by alterations in the calcium concentration of the bathing medium.

Rabbit and guinea pig atrial pairs were tested in 0.9, 1.8, and 3.6 mM calcium Tyrodes using histamine chronotropic dose response curves, before and after treatment with cimetidine or diphenhydramine. Increased calcium levels alone caused an increase in spontaneous rate: the rate of rabbit atria increased 27 beats/min, and that of guinea pig atria 29 beats/min, between the 0.9 and 3.6 mM levels. Both H1-and H2-blockers tested with rabbit atria caused competitive inhibition in 0.9 mM Tyrodes and noncompetitive inhibition in 1.8 mM Tyrodes. In the in 3.6 mM medium, before blockade, the concentration of histamine needed to cause a half maximum increase in rate doubled, strongly suggesting a decrease in histamine's affinity for its receptor. In addition, after blockade, cimetidine acted as a competitive inhibitor, but diphenhydramine did not. In contrast, the guinea pig atria responses were not much affected by the calcium concentration in the bathing medium. Both blockers appeared to act as competitive inhibitors, except in 1.8 mM calcium Tyrodes, in which diphenhydramine acted as a noncompetitive inhibitor. Rabbit atria have both H1- and H2-chronotropic histamine receptors, while guinea pig chronotropic receptors are predominantly of the H2 type. This data suggests that binding to the H1-receptor is in part dependent on calcium while H2-receptor binding appears to be relatively independent of calcium.