Physiological and pharmacological properties of 5-HT3 receptors--a patch clamp-study.
Whole cell and patch clamp techniques were used to investigate the properties of 5-HT3 receptors of a murine neuroblastoma cell line (N1E-115) and adult rabbit nodose ganglion neurones. In addition, some preliminary results from guinea-pig nodose ganglion neurones are presented. In such cells, voltage-clamped at -60 mV, 5-HT (10 microM) induced an inward current associated with a conductance increase. The results of ion substitution experiments suggest that the 5-HT activated ion channel is permeable to both Na+ and K+ ions with a permeability ratio (PNa/PK) of 0.94 and 0.92 for rabbit nodose ganglion cells and N1E-115 cells respectively. On outside out membrane patches excised from rabbit nodose ganglion neurones, 5-HT (1 microM) activated clearly discernible single channel currents with a conductance of 16.6 +/- 0.7 pS (n = 4). In contrast, fluctuation analysis of 5-HT induced whole cell currents suggests that the single channel conductance of N1E-115 cells is only 0.3 pS, a value some 50 fold lower. The 5-HT-induced whole cell currents recorded from all three preparations were antagonised by the selective 5-HT3 receptor antagonist ondansetron (GR38032F) and by the less selective agents metoclopramide, cocaine and (+)-tubocurarine. However, these preparations demonstrate a differential sensitivity to some antagonists. In particular, (+)-tubocurarine was a potent antagonist in N1E-115 cells (IC50 = 0.85 nM) but was approximately 200 fold (IC50 = 156 nM) and 1200 fold (IC50 = 10 microM) less potent in rabbit and guinea-pig nodose ganglion neurones respectively. Additionally, a novel effect of ketamine (10 microM) to potentiate the 5-HT-induced current of rabbit nodose ganglion neurones is described.
Malone
H M
HM
Department of Pharmacology and Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee.
Peters
J A
JA
Lambert
J J
JJ
D000200:Action Potentials; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D005724:Ganglia; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D008787:Metoclopramide / Q000494:pharmacology; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism*; D017294:Ondansetron; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists; D012964:Sodium / Q000378:metabolism; D014403:Tubocurarine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007093:Imidazoles; D007473:Ion Channels; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D017294:Ondansetron; D007649:Ketamine; D012964:Sodium; D003042:Cocaine; D008787:Metoclopramide; D011188:Potassium; D014403:Tubocurarine