Heterogeneity of nicotinic acetylcholine receptor expression in the caudal nucleus of the solitary tract.
The nucleus of the solitary tract (NTS) is the principal integrating relay in the processing of visceral sensory and gustatory information. In the present study, patch-clamp electrophysiological experiments were conducted using rat horizontal brainstem sections. Pre-synaptic and somatic/dendritic nicotinic acetylcholine receptors (nAChRs) expressed in neurons of the caudal NTS (cNTS) were found to be randomly distributed between pre-synaptic and somatic/dendritic sites (chi(2)=0.72, df=3, p>0.87, n=200). Pre-synaptic nAChRs were detected by their facilitating effects on glutamatergic neurotransmission of a sub-population of cNTS neurons (categorized as "effect-positive") upon brief picospritzer applications of 0.1-0.5mM nicotine. These effects were resistant to inhibition by 20nM methyllycaconitine (MLA) and 4muM dihydro-beta-erythroidine (DHbetaE), and were replicated by brief picospritzer applications of 0.2-1mM cytisine. Picospritzer applications of 0.2mM RJR-2403, a potent agonist of alpha4beta2 nAChRs, did not facilitate synaptic release of glutamate in effect-positive cNTS neurons. The population of somatic/dendritic nAChRs has been found to be heterogeneous and included nAChRs that were activated by RJR-2403 and/or cytisine, or insensitive to cytisine, or inhibited by MLA. The presented results are consistent with the expression of beta4-containing (i.e., beta4*) nAChRs, likely alpha3beta4*, in pre-synaptic terminals of effect-positive cNTS neurons. Somatic/dendritic nAChRs appear to involve both alpha7 and non-alpha7 subunits. Heterogeneity in the subunit composition of pre-synaptic and somatic/dendritic nAChRs may underlie diverse roles that these receptors play in regulation of behavioral and visceral reflexes, and may reflect specific targeting by endogenous nicotinic agents and nicotine.
Smith
David V
DV
Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN, USA.
Uteshev
Victor V
VV
D000465:Algorithms; D000818:Animals; D003627:Data Interpretation, Statistical; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D007478:Iontophoresis; D008239:Lysine / Q000031:analogs & derivatives; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579165:Chrna7 protein, rat; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; C013411:biocytin; D008239:Lysine