Regulation of neuronal function by choline and 4OH-GTS-21 through α7 nicotinic receptors

Victor V. Uteshev-Gaard, Edwin M. Meyer, Roger L. Papke

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

A unique feature of α7 nicotinic acetylcholine receptor physiology is that, under normal physiological conditions, α7 receptors are constantly perfused with their natural selective agonist, choline. Studying neurons of hypothalamic tuberomammillary (TM) nucleus, we show that choline and the selective α7 receptor agonist 4OH-GTS-21 can regulate neuronal functions directly, via activation of the native α7 receptors, and indirectly, via desensitizing those receptors or transferring them into a state "primed" for desensitization. The direct action produces depolarization and thereby increases the TM neuron spontaneous firing (SF) rate. The regulation of the spontaneous firing rate is robust in a nonphysiological range of choline concentrations >200 μM. However, modest effects persist at concentrations of choline that are likely to be attained perineuronally under some conditions (20-100 μM). At high physiological concentration levels, the indirect choline action reduces or even eliminates the responsiveness of α7 receptors and their availability to other strong cholinergic inputs. Similarly to choline, 4OH-GTS-21 increases the TM neuron spontaneous firing rate via activation of α7 receptors, and this regulation is robust in the range of clinically relevant concentrations of 4OH-GTS-21. We conclude that factors that regulate choline accumulation in the brain and in experimental slices such as choline uptake, hydrolysis of ACh, membrane phosphatidylcholine catabolism, and solution perfusion rate influence α7 nAChR neuronal and synaptic functions, especially under pathological conditions such as stroke, seizures, Alzheimer's disease, and head trauma, when the choline concentration in the CSF is expected to rise.

Original languageEnglish
Pages (from-to)1797-1806
Number of pages10
JournalJournal of neurophysiology
Volume89
Issue number4
DOIs
StatePublished - 1 Apr 2003

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Nicotinic Receptors
Choline
Neurons
Lateral Hypothalamic Area
3-(4-hydroxy-2-methoxybenzylidene)anabaseine
Phosphatidylcholines
Craniocerebral Trauma
Cholinergic Agents
Alzheimer Disease
Seizures
Hydrolysis
Perfusion
Stroke
Membranes
Brain

Cite this

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Regulation of neuronal function by choline and 4OH-GTS-21 through α7 nicotinic receptors. / Uteshev-Gaard, Victor V.; Meyer, Edwin M.; Papke, Roger L.

In: Journal of neurophysiology, Vol. 89, No. 4, 01.04.2003, p. 1797-1806.

Research output: Contribution to journalArticle

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