DEQUALINIUM, A SELECTIVE BLOCKER OF THE SLOW AFTERHYPERPOLARIZATION IN RAT SYMPATHETIC NEURONS 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 mu M and in voltage clamp experiments, 1 mu M dequalinium produced 45% inhibition of the underlying current I-AHP. When the small conductance Ca2+-activated K+ channels were blocked by 20 nM apamin the slow component of the AHP was abolished, and dequalinium (10 mu M) produced no further change in the residual AHP. Dequalinium (10 mu M) 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 I-K and I-C were all unaffected by 10 mu M 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 Ca2+-activated K+ channel in rat sympathetic neurones.