title: 5-Hydroxytryptamine responses in immature rat rostral ventrolateral medulla neurons in vitro.
abstract: Whole cell patch recordings were made from rostral ventrolateral medullar (RVLM) neurons of brain-stem slices from 8- to 12-day-old rats. By superfusion or pressure ejection to RVLM neurons, 5-hydroxytryptamine (5-HT) elicited three types of membrane potential changes: a slow hyperpolarization (5-HTH), a slow depolarization (5-HTD) and a biphasic response, which persisted in a tetrodotoxin (TTX, 0.3 microM)-containing solution. 5-HTH were accompanied by a decrease of input resistance in the majority of responsive neurons. Hyperpolarization reduced and depolarization increased the 5-HTH; the mean reversal potential was -92.3 mV in 3.1 mM and shifted to -69.3 mV in 7 mM [K+]o. Barium (Ba2+, 0.1 mM) but not tetraethylammonium (TEA, 10 mM) suppressed 5-HTH. The 5-HT1A receptor agonist (+/-)-8-hydroxy-dipropylamino-tetralin (8-OH-DPAT; 5-50 microM) hyperpolarized RVLM neurons. The 5-HT1A antagonist pindobind-5-HT1A (PBD; 1-3 microM) and the 5-HT2/5-HT1 receptor antagonist spiperone (1-10 microM) suppressed 5-HTH and the hyperpolarizing phase of biphasic responses; the 5-HT2 receptor antagonist ketanserin (3 microM) was without significant effect. 5-HTD were associated with an increase or no apparent change of input resistance in RVLM neurons. Hyperpolarization of the membrane decreased or caused no apparent change in 5-HTD. 5-HTD were reduced in an elevated [K+]o (7.0 mM) solution and > 60% in a low Na+ (26 mM) solution and were not significantly changed in a low Cl- (6.7 mM) or Ca(2+)-free/high Mg2+ (10.9 mM) solution. The 5-HT2 receptor agonist alpha-methyl-5-HT (50 microM) depolarized RVLM neurons, and the 5-HT2 antagonist ketanserin (1-10 microM) attenuated the 5-HTD and the depolarizing phase of biphasic responses, whereas the 5-HT1A receptor antagonist PBD (2 microM) was without effect. Inclusion of the hydrolysis resistant guanine nucleotide GDP-beta-S in patch solution significantly reduced the 5-HTH as well as the 5-HTD. The present study shows that, in the immature rat RVLM neurons, 5-HT causes a slow hyperpolarization and depolarization probably by interacting with 5-HT1A and 5-HT2 receptors, which are G-proteins coupled. 5-HTH may involve an increase of an inwardly rectifying K+ conductance, and 5-HTD appear to be caused by a decrease of K+ conductance and/or increase of nonselective cation conductance.
authors.affiliation: Department of Anatomy and Neurobiology, Medical College of Ohio, Toledo 43614, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Hwang
authors.forename: N J
authors.initials: NJ
authors.lastname: Dun
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000502:physiology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008526:Medulla Oblongata / Q000737:chemistry* / Q000166:cytology / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D018492:Dopamine Antagonists; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D012701:Serotonin; D013134:Spiperone; C023427:guanosine 5'-O-(2-thiodiphosphate); D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D019204:GTP-Binding Proteins