Interactions of atropine with heterologously expressed and native α3 subunit-containing nicotinic acetylcholine receptors

Atropine, a classical muscarinic antagonist, has been reported previously to inhibit neuronal nicotinic acetylcholine receptors (nAChRs). In the present study, the action of atropine has been examined on α3β4 receptors expressed heterologously in Xenopus oocytes and native nAChRs in medial habenula neurons. At concentrations of atropine often used to inhibit muscarinic receptors (1 μM), responses induced by near-maximal nicotine concentrations (100 μM) at negative holding potentials (−65 mV) are inhibited (14–30%) in a reversible manner in both α4 and α3 subunit-containing heteromeric nAChRs. Half-maximal effective concentrations (IC50 values) for atropine inhibition are similar for the four classes of heteromeric receptors studied (4–13 μM). For α3β4 nAChRs in oocytes, inhibition by atropine (10 μM) is not overcome at higher concentrations of agonist, and is increased with membrane hyperpolarization. These results are consistent with non-competitive antagonism – possibly ion channel block. At low concentrations of both nicotine (10 μM) and atropine (