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Modulation of the delayed K+ current by histamine in guinea pig ventricular myocytes

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Summary

The effects of histamine on delayed K+ current (IK) were investigated in patch-clamped single guinea pig ventricular myocytes. Histamine increased IK with a maximal fractional response of 2.7 and a kd of 9.4 × 10−7 mol/l. At a concentration of 10−8 mol/l, histamine did not increase IK significantly, but increased ICa by 52% ± 12%. The voltage-dependence of IK activation, the reversal potential and the time course of the IK tail decay were not changed by histamine. Under pretreatment with 10−4 mol/l of ranitidine, neither histamine (10−6 mol/l) nor 2-pyridylethylamine (10−4 mol/l) caused any sizable increase in IK. When the cell was pretreated with a saturating dose of isoproterenol (10−6 mol/l), histamine did not additively enhance IK. The IK enhancement by 3 × 10−7 mol/l histamine was partially antagonized by concurrent exposure to 5 × 10−6 mol/l carbachol. Whereas, use of a higher concentration of histamine (10−6 mol/l) obscured the inhibitory effect of carbachol. It is concluded that histaminergic action of IK is attributed exclusively to H2 receptor-mediated reactions involving Gs protein and adenylate cyclase.

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Tanaka, H., Furukawa, T., Hayafuji, M. et al. Modulation of the delayed K+ current by histamine in guinea pig ventricular myocytes. Naunyn-Schmiedeberg's Arch Pharmacol 344, 582–588 (1991). https://doi.org/10.1007/BF00170656

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