CHOLINE BLOCKS LARGE-CONDUCTANCE K-CA CHANNELS IN MAMMALIAN SYMPATHETIC NEURONS

Using the outside-out configuration of the patch clamp technique, we examined the effects of externally applied choline chloride (ChCl) on the large-conductance calcium-dependent K+(K-Ca) channel in sympathetic neurones of the rabbit coeliac ganglion. Isotonically replacing the bath sodium chloride by ChCl significantly decreased the unitary current amplitude of the K-Ca channels but did not affect their gating properties. The blocking effect was dose-dependent and required 24 mM ChCl to reach half-reduction of the K-Ca channel conductance (from 134 to 64 pS). In whole-cell voltage-clamped neurones, ChCl activated both nicotinic and muscarinic receptors, which induced various membrane current changes including Ca2+ current decrease. We therefore tested the effects of the cholinergic agonists acetylcholine and carbachol on excised K-Ca channels. Both agents failed to mimic the blocking effects of ChCl. We therefore conclude that K-Ca channels in sympathetic neurones are occluded by external choline chloride.