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

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 x 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 x 10(-7) mol/l histamine was partially antagonized by concurrent exposure to 5 x 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.