On the mechanism of histamine induced enhancement of the cardiac Ca2+ current
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- Hescheler, J., Tang, M., Jastorff, B. et al. Pflugers Arch. (1987) 410: 23. doi:10.1007/BF00581891
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In guinea pig ventricular myocytes, the effect of histamine on the slow Ca2+ current (ICa) was studied and the following results were obtained: (1) Superfusion of cells with histamine resulted in a dose-dependent enhancement of the amplitude of ICa. The threshold concentration of histamine was 10−8 M, half maximal increase occurred at 3×10−7 M and maximal enhancement (about 3–4-fold) at 5×10−6 M. (2) The histamine effect was greatly reduced by the H2 antagonist cimetidine (10−5 M) but only slightly by the H1 antagonist diphenhydramine (10−5M). (3) Effects of isoprenaline (ISP) and histamine at maximal effective concentrations on ICa were not additive, suggesting that both agents use the same intracellular pathway. Intracellular infusion of a blocker of the cAMP-dependent protein kinase, Rp-cAMPS (10−4 M), prevented the histamine effect. (4) The involvement of GTP-dependent transducer proteins was studied by cell dialysis with several GTP derivatives. Intracellular application of the stable GDP-analogue, GDP-β-S, reduced the histamine effect on ICa, whereas the stable GTP analogue, GTP-γ-S, mimicked the histamine effect.