title: Functional expression of α7-nicotinic acetylcholine receptors by muscle afferent neurons.
abstract: The exercise pressor reflex (EPR) is generated by group III and IV muscle afferents during exercise to increase cardiovascular function. Muscle contraction is triggered by ACh, which is metabolized into choline that could serve as a signal of exercise-induced activity. We demonstrate that ACh can induce current in muscle afferents neurons isolated from male Sprague-Dawley rats. The nicotinic ACh receptors (nAChRs) appear to be expressed by some group III-IV neurons since capsaicin (TRPV1) and/or ATP (P2X) induced current in 56% of ACh-responsive neurons. α7- And α4β2-nAChRs have been shown to be expressed in sensory neurons. An α7-nAChR antibody stained 83% of muscle afferent neurons. Functional expression was demonstrated by using the specific α7-nAChR blockers α-conotoxin ImI (IMI) and methyllycaconitine (MLA). MLA inhibited ACh responses in 100% of muscle afferent neurons, whereas IMI inhibited ACh responses in 54% of neurons. Dihydro-β-erythroidine, an α4β2-nAChR blocker, inhibited ACh responses in 50% of muscle afferent neurons, but recovery from block was not observed. Choline, an α7-nAChR agonist, elicited a response in 60% of ACh-responsive neurons. Finally, we demonstrated the expression of α7-nAChR by peripherin labeled (group IV) afferent fibers within gastrocnemius muscles. Some of these α7-nAChR-positive fibers were also positive for P2X3 receptors. Thus choline could serve as an activator of the EPR by opening α7-nAChR expressed by group IV (and possible group III) afferents. nAChRs could become pharmacological targets for suppressing the excessive EPR activation in patients with peripheral vascular disease.
authors: The Baker Laboratory of Pharmacology, Department of Pharmacology, Kirksville College of Osteopathic Medicine, A.T. Still University of Health Sciences, Kirksville, Missouri.
authors: James C
authors: JC
authors: Baxter
authors: The Baker Laboratory of Pharmacology, Department of Pharmacology, Kirksville College of Osteopathic Medicine, A.T. Still University of Health Sciences, Kirksville, Missouri.
authors: Renuka
authors: R
authors: Ramachandra
authors: The Baker Laboratory of Pharmacology, Department of Pharmacology, Kirksville College of Osteopathic Medicine, A.T. Still University of Health Sciences, Kirksville, Missouri.
authors: Dustin R
authors: DR
authors: Mayne
authors: The Baker Laboratory of Pharmacology, Department of Pharmacology, Kirksville College of Osteopathic Medicine, A.T. Still University of Health Sciences, Kirksville, Missouri kelmslie@atsu.edu.
authors: Keith S
authors: KS
authors: Elmslie
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D059329:Cholinergic Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D020916:Conotoxins / Q000494:pharmacology; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D020916:Conotoxins; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D002211:Capsaicin; D000157:Aconitine
keywords: P2X; TRPV1; choline; exercise pressor reflex; α4β2