Ketanserin, a 5-HT2 antagonist, directly inhibits the ATP-sensitive potassium channel in mouse ventricular myocytes.
The effects of ketanserin, a 5-HT2 antagonist, on the ATP-sensitive K+ (K(ATP)) channels were studied in mouse ventricular myocytes using patch clamp technique. Under the whole-cell voltage clamp conditions, ketanserin (1-100 microM) reversibly inhibited pinacidil-induced K(ATP) current in a concentration-dependent fashion with a Ki value of 9.36 microM and the Hill coefficient was 0.67. This inhibition was developed even with the presence of 5-hydroxytryptamine (100 microM) in the bath. Prazosin, a selective alpha1-antagonist, also failed to mimic the effect of ketanserin. Ketanserin did not affect the channel activity in inside-out configuration under the ATP-free internal solution. Furthermore, ketanserin applied to the external solution did not affect the pinacidil-induced channel activity in the cell-attached patches, but did inhibit it when applied into the pipette. These results suggest that the inhibitory action of ketanserin observed in this study was probably due to a direct action on the K(ATP) channel rather than to an action through the 5-HT2 receptor or alpha1-adrenoceptor blockade, and that the antiarrhythmic activity of ketanserin against cardiac arrhythmias induced in the ischemic/reperfused heart is at least in part attributable to its inhibition of the K(ATP) channel.
Ju
Jeong-Min
JM
Department of Pharmacology, Chonnam National University Medical School, Gwangju, Korea.
Hwang
Jae-Ha
JH
Piao
Ling-Hua
LH
Park
Hyung-Wook
HW
Park
Jong-Seong
JS
Shin
Dong-Ho
DH
Cho
Jeong-Gwan
JG
Kim
Kyung Keun
KK
Kim
Jae-Ha
JH
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D044348:Receptors, Serotonin, 5-HT2 / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018340:Receptors, Adrenergic, alpha-1; D044348:Receptors, Serotonin, 5-HT2; D012702:Serotonin Antagonists; D000255:Adenosine Triphosphate; D007650:Ketanserin