Influence of calcium concentration on the rate of onset of cardiac glycoside and aglycone inotropism.

Isolated rabbit atria were employed to examine the rate of onset of inotropism of two glycosides (strophanthin and ouabain) and aglycones (acetylstrophanthidin and ouabagenin) in the presence of various concentrations of calcium (0.55, 1.1, 2.2, 4.4 and 8.8 mM). The rate of onset of glycoside-induced inotropism was found to be greatly influenced by the calcium concentration. The rate of onset was increased in both low and high calcium, with the minimum rate of onset at 1.1 or 2.2 mM calcium. In contrast, the rate of onset of aglycone-induced inotropism was not dependent on calcium between 0.55 and 4.4 mM calcium. The rate of onset of aglycone-induced inotropism was increased at 8.8 mM calcium. The results are interpreted by postulating that the digitalis inotropic receptor is located in a membrane-limited compartment to which aglycones may gain access via passive diffusion but to which glycosides gain access mainly via a (calcium-dependent) carrier mechanism.