Endogenous activation of nicotinic receptors underlies sympathetic tone generation in neonatal rat spinal cord in vitro.
Without the brainstem, thoracic spinal cords of neonatal rats in vitro spontaneously generate tonic sympathetic nerve discharge (SND) in the splanchnic nerves. Activation of nicotinic receptors in cords is known to alter a repertoire of neurotransmitter releases to sympathetic preganglionic neurons (SPNs). Using in vitro nerve-cord preparations, we investigated whether endogenous nicotinic receptor activity is essential for SND genesis. Application of mecamylamine, an open-channel nicotinic receptor blocker, reduced SND in a progressive manner. Exogenous activation of nicotinic receptors by application of various nicotinic agonists generally excited SND at low agonistic concentrations. At higher concentrations, however, agonists induced biphasic responses characterized by an initial excitation followed by prolonged SND suppression. Whether ionotropic glutamate, GABA(A), or glycine receptors are downstream signals of nicotinic receptor activation was explored by pretreatment of cords with selective antagonists. The initial excitation of SND persisted in the presence of ionotropic glutamate receptor antagonists. In contrast, the SND suppression was partially reversed by glycine or GABA(A) receptor antagonists. Incubation of the cord in a low Ca(2+)/high Mg(2+) bath solution to block Ca(2+)-dependent synaptic transmission did not affect SND excitation induced by nicotinic agonists, confirming direct activation of postsynaptic nicotinic receptors on SPNs. In conclusion, the endogenous activity of nicotinic receptors is essential for SND genesis in the thoracic spinal cord. Nicotinic activation of glycinergic and GABAergic interneurons may provide a recurrent inhibition of SPNs for homeostatic regulation of sympathetic outflow.
Chen
Hsin-Kai
HK
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan.
Su
Chun-Kuei
CK
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects* / Q000502:physiology; D002799:Cholinergic Fibers / Q000502:physiology; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D005998:Glycine / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D007736:Kynurenic Acid / Q000494:pharmacology; D008464:Mecamylamine / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000502:physiology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D063065:Organophosphonates / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D013153:Splanchnic Nerves / Q000502:physiology*; D017779:Sympathetic Fibers, Postganglionic / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000157:Aconitine; D004079:Dihydro-beta-Erythroidine; D004246:Dimethylphenylpiperazinium Iodide; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D005998:Glycine; D007736:Kynurenic Acid; D008464:Mecamylamine; D009419:Nerve Tissue Proteins; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D063065:Organophosphonates; D010649:Phenylalanine; D010852:Picrotoxin; D011978:Receptors, Nicotinic; C091378:3-(2'-phosphonomethyl(1,1'-biphenyl)-3-yl)alanine; C403530:nicotinic receptor alpha3beta4; C054634:methyllycaconitine