MOLECULAR PHARMACOLOGY, 34:421-426 ACCELERA TED COMMUNICATION Cloned Muscarinic Receptor Subtypes Expressed in A9 L Cells Differ in Their Coupling to Electrical Responses

The electrophysiological responses to cholinergic stimulation of four cloned muscannic receptor subtypes (ml-m4) were studied in A9 L cells transfected with the expression plasmids of each ofthe different subtypes, using the tight-seal whole-cell recording technique. Cells transfected with ml and m3 muscarinic receptor subtypes were hyperpolarized by acetylcholine (ACh), whereas m2- and m4-transfected cells did not respond to ACh concentra-tions of up to 1 m. Stimulation of both ml and m3 muscarinic receptor subtypes evoked outward currents in cells voltage-clamped at-50 mV, associated with an increase in membrane conductance. These outward currents were blocked by atropine but not by tubocurarine. The ACh-induced currents of ml- and m3-transfected cells primarily involved potassium ions, although chloride ions also contributed to a minor extent. The potassium and chloride conductances were blocked by barium or cobal