Modulation by histamine of the delayed outward potassium current in guinea-pig ventricular myocytes.
1. Histamine receptor-mediated modulation of the delayed outward potassium current (IK) was investigated in guinea-pig single ventricular cells by the whole-cell voltage clamp. 2. Histamine increased IK in a dose- dependent manner with a half-maximum dose of 3.8 x 10(-8) M. Histamine (10(-6) M) increased IK by a factor of 3.02 without a significant change in the current kinetics. The threshold dose of histamine for increasing IK was 10(-9) M and this value was similar to that for calcium current. 3. Cimetidine decreased IK in the presence of histamine, by shifting the dose-response curve to histamine to the right. The pA2 value of cimetidine against histamine was 6.38. 4. Forskolin did not increase IK after application of 10(-6) M histamine, and histamine scarcely increased IK in the presence of a heat-stable inhibitor of cyclic AMP-dependent protein kinase (PKI). 5. We conclude that stimulation by histamine of IK is mainly by way of the H2-receptor, and is mediated by cyclic AMP-dependent phosphorylation.
Yazawa
K
K
Department of Pharmacology, Asahikawa Medical College, Japan.
Abiko
Y
Y
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D011494:Protein Kinases / Q000494:pharmacology; D012964:Sodium / Q000502:physiology
D015220:Calcium Channels; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D015221:Potassium Channels; D005576:Colforsin; D006632:Histamine; D012964:Sodium; D011494:Protein Kinases; D011188:Potassium