Introduction: In transgenic mice (TG) which overexpress the human H2 histamine receptor specifically in cardiomyocytes by means of the alpha MHC promoter but not in wild type litter mice (WT) the H2 receptor agonist dimaprit can exert positive inotropic and chronotropic effects. Moreover, we have previously shown in the presence of dimaprit the incidence of arrhythmias in right atrial preparations was higher in TG than in WT.
Case presentation: The dimaprit-induced arrhythmias in right atrial preparations of TG could be attenuated by subsequent addition of the H2 receptor antagonist cimetidine (10µM, 4/4, p < 0.05). Furthermore, the protein kinase A inhibitor H89 and the CAM-kinase inhibitor W7 reduced the dimaprit induced positive inotropic effect in TG left atrial preparations (H89: 50µM, 7/7, p < 0.05; W7: 50µM, 12/12, p < 0.05) and did not reduce the incidence of dimaprit-induced arrhythmias in right atrial preparations of TG. SQ 22536 is an adenylate cyclase inhibitor and induced arrhythmias only in TG but not WT right atrial preparations, and intensified dimaprit-induced arrhythmias in TG right arterial preparations (50µM, 5/7, p<0.05).
Conclusions: In summary, we detected dimaprit induced arrhythmias in TG were H2-receptor antagonist-sensitive but not sensitive to the tested kinase inhibitors. This is indicative of a direct effect of H2-receptors on arrhythmogenic ion channels, not involving ion channel phosphorylation.