Effect of histamine on cardiac sarcolemmal calcium binding as indicated by use of ionic lanthanum

To determine whether the inotropic effect of histamine might be associated with enhanced calcium binidng to the sarcolemmal-glycocalyx complex, the effect of histamine on lanthanum binding to the cell membrane in the presence of verapamil was assessed. Rabbit hearts were perfused firstly with histamine, secondly with histamine and verapamil, and subsequently with histamine in the presence of lanthanum and verapamil. Subsequent transmission electron microscopy showed the presence of bound lanthanum on both the cellular surface and cytoplasmic vesicles of most cardiac myocytes, which is in contrast to the absence of lanthanum binding that occurs in the presence of verapamil alone. Furthermore, this histamine mediated enhancement of lanthanum binding is not affected by the H₁ antagonist diphenhydramine but is reduced by the H₂ antagonist cimetidine. This visual evidence of an apparent enhancement of lanthanum binding under histamine and subsequent attenuation with cimetidine supports the hypothesis that histamine may exert its positive inotropic effect by causing increased calcium binding to the sarcolemmal-glycocalyx complex of cardiac muscle and that the effect is mediated at least in part by H₂ receptors.