Relative contribution of SK <inf>Ca</inf> and TREK1 channels in purinergic and nitrergic neuromuscular transmission in the rat colon

V. Gil, D. Gallego, H. Moha Ou Maati, R. Peyronnet, M. Martínez-Cutillas, C. Heurteaux, M. Borsotto, M. Jiménez

Research output: Contribution to journalArticleResearchpeer-review

21 Citations (Scopus)

Abstract

Purinergic and nitrergic neurotransmission predominantly mediate inhibitory neuromuscular transmission in the rat colon. We studied the sensitivity of both purinergic and nitrergic pathways to spadin, a TWIK-related potassium channel 1 (TREK1) inhibitor, apamin, a small-conductance calcium-activated potassium channel blocker and 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ), a specific inhibitor of soluble guanylate cyclase. TREK1 expression was detected by RT-PCR in the rat colon. Patch-clamp experiments were performed on cells expressing hTREK1 channels. Spadin (1 μM) reduced currents 1) in basal conditions 2) activated by stretch, and 3) with arachidonic acid (AA; 10 μM). L-Methionine (1 mM) or L-cysteine (1 mM) did not modify currents activated by AA. Microelectrode and muscle bath studies were performed on rat colon samples. L-Methionine (2 mM), apamin (1 μM), ODQ (10 μM), and N ω-nitro-L-arginine (L-NNA; 1 mM) depolarized smooth muscle cells and increased motility. These effects were not observed with spadin (1 μM). Purinergic and nitrergic inhibitory junction potentials (IJP) were studied by incubating the tissue with L-NNA (1 mM) or MRS2500 (1 μM). Both purinergic and nitrergic IJP were unaffected by spadin. Apamin reduced both IJP with a different potency and maximal effect for each. ODQ concentration dependently abolished nitrergic IJP without affecting purinergic IJP. Similar effects were observed in hyperpolarizations induced by sodium nitroprusside (1 μM) and nitrergic relaxations induced by electrical stimulation. We propose a pharmacological approach to characterize the pathways and function of purinergic and nitrergic neurotransmission. Nitrergic neurotransmission, which is mediated by cyclic guanosine monophosphate, is insensitive to spadin, an effective TREK1 channel inhibitor. Both purinergic and nitrergic neurotransmission are inhibited by apamin but with different relative sensitivity. © 2012 the American Physiological Society.
Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume303
DOIs
Publication statusPublished - 1 Aug 2012

Keywords

  • Apamin
  • Gastrointestinal
  • ODQ
  • Smooth muscle
  • Spadin

Fingerprint Dive into the research topics of 'Relative contribution of SK <inf>Ca</inf> and TREK1 channels in purinergic and nitrergic neuromuscular transmission in the rat colon'. Together they form a unique fingerprint.

  • Cite this

    Gil, V., Gallego, D., Moha Ou Maati, H., Peyronnet, R., Martínez-Cutillas, M., Heurteaux, C., Borsotto, M., & Jiménez, M. (2012). Relative contribution of SK <inf>Ca</inf> and TREK1 channels in purinergic and nitrergic neuromuscular transmission in the rat colon. American Journal of Physiology - Gastrointestinal and Liver Physiology, 303. https://doi.org/10.1152/ajpgi.00040.2012