Dequalinium, a selective blocker of the slow afterhyperpolarization in rat sympathetic neurones in culture.
The actions of dequalinium have been investigated in cultured rat sympathetic neurones. It produced a rapid and reversible inhibition of the slow apamin-sensitive component of the afterhyperpolarization (AHP) which follows a single action potential in these cells. The IC50 for this effect was 1.1 microM and in voltage clamp experiments, 1 microM dequalinium produced 45% inhibition of the underlying current IAHP. When the small conductance Ca(2+)-activated K+ channels were blocked by 20 nM apamin the slow component of the AHP was abolished, and dequalinium (10 microM) produced no further change in the residual AHP. Dequalinium (10 microM) had no effect on the voltage-activated Ca2+ current in these cells, suggesting that the inhibition of the AHP was the result of a direct interaction with the K+ channels. The A-current as well as a composite current made up of IK and IC were all unaffected by 10 microM dequalinium. However, at this concentration it did produce 18% inhibition of the M-current. These results show dequalinium to be a potent and selective non-peptide blocker of the apamin-sensitive small conductance Ca(2+)-activated K+ channel in rat sympathetic neurones.
Dunn
P M
PM
Department of Pharmacology, University College London, UK.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D003868:Dequalinium / Q000494:pharmacology*; D004594:Electrophysiology; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects*
D015221:Potassium Channels; D001030:Apamin; D003868:Dequalinium; D002118:Calcium