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An electrophysiological investigation of the properties of 5‐HT 3 receptors of rabbit nodose ganglion neurones in culture
Author(s) -
Peters John A.,
Malone Hilary M.,
Lambert Jeremy J.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13863.x
Subject(s) - nodose ganglion , electrophysiology , biophysics , patch clamp , conductance , chemistry , ion channel , 5 ht receptor , membrane potential , methysergide , reversal potential , serotonin , receptor , endocrinology , medicine , biology , vagus nerve , biochemistry , stimulation , mathematics , combinatorics
1 The biophysical and pharmacological properties of 5‐hydroxytryptamine (5‐HT)‐evoked currents in rabbit nodose ganglion neurones in culture have been determined by use of the whole‐cell and outside‐out membrane patch recording modes of the patch‐clamp technique. 2 In 49% of cells investigated the bath application of 10 −5 m 5‐HT at negative holding potentials elicited an inward current. The whole‐cell response to 5‐HT reversed in sign (E 5‐HT ) at approximately − 2 mV and exhibited inward rectification. 3 The influence of various ion substitutions upon E 5‐HT established that the 5‐HT‐evoked current is mainly mediated by a mixed Na + , K + cation conductance with little or no contribution from Cl − ions. The omission of Ca 2+ and Mg 2+ from the extracellular solution enhanced the amplitude of the 5‐HT‐induced current. 4 On isolated outside‐out membrane patches, the bath application of 10 −6 m 5‐HT induced single channel currents with a chord conductance of approximately 17 pS at − 70 mV and an average slope conductance of 19 pS over the range − 100 to − 40 mV. The 5‐HT‐induced single channels exhibited modest inward rectification and were reduced in frequency, but not amplitude, by the 5‐HT 3 receptor antagonist metoclopromide (10 −6 m ). 5 The bath application of 5‐HT (3 × 10 −7 − 3 × 10 −5 m ) to whole cells voltage clamped at − 60 mV produced dose‐dependent inward currents which were mimicked by 2‐methyl‐5‐HT and 1‐phenylbiguanide with equipotent molar ratios, relative to 5‐HT, of 2.5 and 32 respectively. 6 Whole‐cell inward currents produced by the local pressure application of 5‐HT (10 −5 m ) were unaffected by 10 −6 m methysergide, 10 −6 m ketanserin or 10 −6 m citalopram, but were concentration‐dependently antagonized by the selective 5‐HT 3 receptor antagonists tropisetron (IC 50 = 4.6 × 10 −11 m ) ondansetron (IC 50 = 5.7 × 10 −11 m ), and bemesetron (IC 50 = 3.3 × 10 −10 m ). The response to 5‐HT was also blocked by the non‐selective antagonists metoclopramide (IC 50 = 1.2 × 10 −8 m ), cocaine (IC 50 = 8.3 × 10 −8 m ) and (+)‐tubocurarine (IC 50 = 1.6 × 10 −7 m ).