title: Effect of cholinergic agonists on bulbospinal C1 neurons in rats.
abstract: Cholinergic inputs to the rostral ventrolateral medulla (RVLM) may contribute to sympathetic tone generation. The present study analyzes the response of RVLM neurons to cholinergic agonists. In chloralose-anesthetized rats iontophoresis of carbachol excited RVLM sympathoexcitatory neurons (+69% from resting level of 11.9 +/- 2 spikes/s; n = 28). This effect was reduced 85% by iontophoresis of methylatropine and abolished by intravenous scopolamine. Iontophoresis of nicotine or hexamethonium was ineffective. In contrast, most RVLM respiratory units were inhibited by carbachol. Whole cell recordings of bulbospinal RVLM neurons were made in neonatal rat brain slices (54 cells, 24 C1 adrenergic neurons). In current-clamp recordings (without tetrodotoxin) carbachol produced depolarization, increased postsynaptic potential frequency, and decreased input resistance. In voltage-clamp recording (-50 to -60 mV; 1 microM tetrodotoxin) carbachol produced inward current [50% effective concentration (EC50): 10 +/- 1 microM; 12.6 +/- 2 pA at 30 microM; n = 16] that persisted in low Ca2+/high Mg2+ (n = 6). Muscarine (30 microM) caused smaller inward currents (2.6 +/- 0.6 pA; n = 16). The carbachol-induced current was reduced 46% by 5 microM methylatropine (n = 15) and 84% by 200 microM hexamethonium (n = 9). The current was linear as a function of the holding potential (extrapolated reversal potential: -22 +/- 2 mV). In conclusion, carbachol exerts both pre- and postsynaptic effects on C1 and other putative sympathoexcitatory RVLM neurons. In vitro the postsynaptic effect of carbachol has a mixed nicotinic and muscarinic pharmacology. In vivo, iontophoretically applied carbachol produces muscarinic excitation of barosensitive RVLM neurons.
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville 22908, USA.
authors.forename: D
authors.initials: D
authors.lastname: Huangfu
authors.forename: M
authors.initials: M
authors.lastname: Schreihofer
authors.forename: P G
authors.initials: PG
authors.lastname: Guyenet
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology*; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009116:Muscarine / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D014666:Vasomotor System / Q000166:cytology / Q000187:drug effects
chemical_list: D018679:Cholinergic Agonists; D013779:Tetrodotoxin; D009116:Muscarine; D002217:Carbachol