Otilonium bromide inhibits muscle contractions via L-type calcium channels in the rat colon

M. T. Martin, L. Hove-Madsen, M. Jimenez

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17 Citations (Scopus)

Abstract

The aim of this study is to evaluate in vitro the effect of otilonium bromide (OB) on the mechanical and electrical activities of the rat colonic smooth muscle using muscle bath, microelectrodes and patch-clamp techniques. Otilonium bromide dose dependently inhibited the spontaneous activity (logIC50 ± SE: -5.31 ± 0.05). This effect was not modified by TTX (10-6 mol L-1). Cyclic depolarizations were abolished by OB (10-4 mol L-1). Electrical field stimulation induced inhibitory junction potentials (IJPs) followed by a depolarization with super-imposed spikes causing a contraction. In the presence of OB (10-4 mol L-1) IJPs were recorded, but spikes and contractions were abolished. Otilonium bromide (3 × 10-6 mol L-1) inhibited inward current obtained in isolated cells (amphotericin perforated patch technique). The otilonium-sensitive current amplitude was maximal (75pA) around 0 mV. The effect of different doses of OB was tested by depolarizing cells from -70 mV to 0 mV. OB dose dependently inhibited the inward current with an EC50 of 885 nmol L-1. Abolishment of the otilonium-sensitive current by 3 × 10-6 mol L-1 nifedipine confirmed that it was an L-type Ca2+ current. Our results show that OB inhibits the spontaneous and triggered muscular contractions. This effect is produced by the inhibition of muscular action potentials carried by L-type calcium current, confirming the spasmolytic properties of OB.
Original languageEnglish
Pages (from-to)175-183
JournalNeurogastroenterology and Motility
Volume16
DOIs
Publication statusPublished - 1 Apr 2004

Keywords

  • Electrophysiology
  • Muscle bath
  • Otilonium bromide
  • Patch-clamp
  • Rat colon

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