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7 nicotinic receptors
* To whom correspondence should be addressed. E-mail: rpapke{at}college.med.ufl.edu.
A unique feature of 
7 nicotinic acetylcholine receptor physiology is that under normal physiological conditions, 7 receptors are constantly perfused with their natural selective agonist, choline. Studying neurons of hypothalamic tuberomammillary (TM) nucleus, we show that choline and the selective 7 receptor agonist 4OH-GTS-21 can regulate neuronal functions directly, via activation of the native 7 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 non-physiological 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 7 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 7 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 experimental slices such as choline uptake, hydrolysis of ACh, membrane phosphatidylcholine catabolism, and solution perfusion rate influence 7 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.
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