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

Academic Article

Abstract

  • 1. 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. 2. 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 (IC 50 values) for atropine inhibition are similar for the four classes of heteromeric receptors studied (4-13 μM). 3. 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. 4. At low concentrations of both nicotine (10 μM) and atropine (< 10 μM), potentiation (≈ 25%) of α3β4 nAChR responses in oocytes is observed. The relative balance between potentiation and inhibition is dependent upon membrane potential. 5. In rat medial habenula (MHb) neurons, atropine (0.3-3.0 μM) inhibited nicotine-induced responses in both a concentration and membrane potential-dependent manner (at -40 mV, IC 50=4 μM), similar to the effects on α3β4-nAChRs in oocytes. However, unlike heterologously expressed receptors, potentiation was barely detectable at depolarized membrane potentials using low concentrations of nicotine (3-10 μM). Conversely, the weak agonist, choline (1-3 mM) was observed to augment responses of MHb nAChRs.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Parker JC; Sarkar D; Quick MW; Lester RAJ
  • Start Page

  • 801
  • End Page

  • 810
  • Volume

  • 138
  • Issue

  • 5