Imipramine, mianserine and maprotiline block delayed rectifier potassium current in ventricular myocytes.
Imipramine, mianserine and maprotiline are three widely used antidepressant drugs with different chemical structure. In the present work we have studied the effects of these drugs on the delayed rectifier potassium current (I(K)) in myocytes isolated from rat ventricle. The delayed rectifier potassium current, responsible for action potential termination, is blocked by all of the three drugs I(K)studied in a state-independent manner. Imipramine and mianserine block I(K)in a 1 : 1 drug-receptor interaction, whereas maprotiline shows a negative cooperativity in the interaction between the channel complex and drug molecules.
Casis
Oscar
O
Department of Physiology, School of Pharmacy, University of the Basque Country, Bilbao, Spain. ofpcasao@lg.ehu.es
Gallego
Mónica
M
Sánchez-Chapula
José A
JA
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D051668:Delayed Rectifier Potassium Channels; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000166:cytology; D007099:Imipramine / Q000494:pharmacology*; D008376:Maprotiline / Q000494:pharmacology*; D008803:Mianserin / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D017208:Rats, Wistar; D016276:Ventricular Function
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D051668:Delayed Rectifier Potassium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D008803:Mianserin; D008376:Maprotiline; D007099:Imipramine