An electrophysiological investigation of the properties of 5‐HT3 receptors of rabbit nodose ganglion neurones in culture

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Abstract

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. 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 (E5‐HT) at approximately − 2 mV and exhibited inward rectification. The influence of various ion substitutions upon E5‐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 Ca2+ and Mg2+ from the extracellular solution enhanced the amplitude of the 5‐HT‐induced current. 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‐HT3 receptor antagonist metoclopromide (10−6 m). 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. 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‐HT3 receptor antagonists tropisetron (IC50 = 4.6 × 10−11 m) ondansetron (IC50 = 5.7 × 10−11 m), and bemesetron (IC50 = 3.3 × 10−10 m). The response to 5‐HT was also blocked by the non‐selective antagonists metoclopramide (IC50 = 1.2 × 10−8 m), cocaine (IC50 = 8.3 × 10−8 m) and (+)‐tubocurarine (IC50 = 1.6 × 10−7 m). 1993 British Pharmacological Society

Original languageEnglish
Pages (from-to)665-676
Number of pages12
JournalBritish Journal of Pharmacology
Volume110
Issue number2
DOIs
Publication statusPublished - Oct 1993

Keywords

  • 5‐HT receptor
  • 5‐HT receptor agonists
  • 5‐HT receptor antagonists
  • 5‐HT receptor electrophysiology
  • 5‐HT receptor‐evoked currents
  • nodose ganglion neurone

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