Desensitization of nicotinic acetylcholine receptors in central nervous system neurons of the stick insect (Carausius morosus) by imidacloprid and sulfoximine insecticides

We used patch-clamp recordings and fast optical Ca2+ imaging to characterize an acetylcholine-induced current ( IACh) in leg motoneurons of the stick insect Carausius morosus. Our long-term goal is to better understand the synaptic and integrative properties of the leg sensory-motor system, which has served extremely successfully as a model to study basic principles of walking and locomotion on the network level. The experiments were performed under biophysically controlled conditions on freshly dissociated leg motoneurons to avoid secondary effects from the network. To allow for unequivocal identification, the leg motoneurons were backfilled with a fluorescent label through the main leg nerve prior to cell dissociation. In 87% of the motoneurons, IACh consisted of a fast-desensitizing ( IACh1) and a slow-desensitizing component ( IACh2), both of which were concentration dependent, with EC50 values of 3.7 × 10−5 and 2.0 × 10−5 M, respectively. Ca2+ imaging revealed that a considerable portion of IACh (∼18%) is carried by Ca2+, suggesting that IACh, besides mediating fast synaptic transmission, could also induce Ca2+-dependent processes. Using specific nicotinic and muscarinic acetylcholine receptor ligands, we showed that IACh was exclusively mediated by nicotinic acetylcholine receptors. Distinct concentration–response relations of IACh1 and IACh2 for these ligands indicated that they are mediated by different types of nicotinic acetylcholine receptors.

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Alpha4beta2 Neuronal Nicotinic Acetylcholine Receptors in the Central Nervous System Are Inhibited by Isoflurane and Propofol, but alpha7-type Nicotinic Acetylcholine Receptors Are Unaffected

Anesthesiology ◽

10.1097/00000542-199704000-00016 ◽

1997 ◽

Vol 86 (4) ◽

pp. 859-865 ◽

Cited By ~ 167

Author(s):

Pamela Flood ◽

Jose Ramirez-Latorre ◽

Lorna Role

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Acetylcholine Receptor ◽

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

General Anesthetics ◽

Nicotinic Acetylcholine ◽

The Central Nervous System ◽

Beta 2 ◽

Alpha 7

Background The mechanisms of action of general anesthetics are not completely understood. Many general anesthetics are reported to potentiate gamma-aminobutyric acid (GABAA) and glycine receptors in the central nervous system (CNS) and to inhibit the muscle-type nicotinic acetylcholine receptor (nAChR). The effects of general anesthetics on another family of ligand-gated ion channel in the CNS, the nAChRs, have not been defined. Methods Two types of CNS acetylcholine receptor, the alpha 4 beta 2 receptor or the alpha 7 homomeric receptor, were expressed heterologously in Xenopus laevis oocytes. Using the standard two-microelectrode voltage-clamp technique, peak acetylcholinegated current was measured before and after coapplication of isoflurane or propofol. Results Coapplication of either isoflurane or propofol with acetylcholine resulted in potent, dose-dependent inhibition of the alpha 4 beta 2 receptor current with median inhibitory concentrations of 85 and 19 microM, respectively. The inhibition of the alpha 4 beta 2 receptor by both isoflurane and propofol appears to be competitive with respect to acetylcholine. The alpha 7 receptor current was not effected by either anesthetic. Conclusions The CNS-type nAChRs are differentially affected by isoflurane and propofol. The alpha 4 beta 2 receptor is affected by isoflurane more potently than the most sensitive GABAA or glycine receptor that has been reported, whereas the alpha 7 homomeric receptor is not affected by either anesthetic. Inhibition of specific subtypes of nAChRs in the CNS, along with potentiation of GABAA and glycine receptors, may contribute to the effects and side effects of general anesthetics.

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