The positive chronotropic effects of Bay K-8644 and calcium as influenced by temperature.

The positive chronotropic effects of the dihydropyridine calcium agonist BAY K-8644 and calcium were studied in spontaneously beating right guinea-pig atria. Within the temperature range from 22 to 37 degrees C, the following observations were made: (1) The basal pacemaker frequency increased linearly with the ambient temperature; (2) the increase in pacemaker rate produced by a maximally effective concentration of BAY K-8644 was of the same magnitude as that produced by calcium; (3) the increases in pacemaker rate produced by BAY K-8644 and by calcium were directly proportional to the increase in temperature above 22 degrees C; and (4) at 37 degrees C, the apparent ED50 for the positive chronotropic effect of calcium was 2.3 X 10(-3) M and of BAY K-8644 was 0.7 X 10(-7) M. At temperatures below 22 degrees C, irregular pacemaking activity or complete arrest of pacemaking activity frequently occurred. The data are in strong support of the assumption that BAY K-8644 elicits its positive chronotropic effect by increasing the availability of calcium ions.