Choline blocks large conductance KCa channels in mammalian sympathetic neurones

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+ (KCa) 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 KCa 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 KCa 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 KCa channels. Both agents failed to mimic the blocking effects of ChCl. We therefore conclude that KCa channels in sympathetic neurones are occluded by external choline chloride.