Purinergic activation of spontaneous transient outward currents in guinea pig taenia colonic myocytes

In Deok Kong, Sang Don Koh, Kenton M. Sanders

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Spontaneous transient outward currents (STOCs) were recorded from smooth muscle cells of the guinea pig taenia coli using the whole cell patch-clamp technique. STOCs were resolved at potentials positive to -50 mV. Treating cells with caffeine (1 mM) caused a burst of outward currents followed by inhibition of STOCs. Replacing extracellular Ca2+ with equimolar Mn2+ caused STOCs to 'run down.' Iberiotoxin (200 nM) or charybdotoxin (ChTX; 200 nM) inhibited large-amplitude STOCs, but small- amplitude 'mini-STOCs' remained in the presence of these drugs. Mini-STOCs were reduced by apamin (500 nM), an inhibitor of small-conductance Ca2+- activated K+ channels (SK channels). Application of ATP or 2- methylthioadenosine 5'-triphosphate (2-MeS-ATP) increased the frequency of STOCs. The effects of 2-MeS-ATP persisted in the presence of charybdotoxin but were blocked by combination of ChTX (200 nM) and apamin (500 nM). 2-MeS- ATP did not increase STOCs in the presence of pyridoxal phosphate 6- azophenyl-2',4'-disulfonic acid, a P2 receptor blocker. Similarly, pretreatment of cells with U-73122 (1 μM), an inhibitor of phospholipase C (PLC), abolished the effects of 2-MeS-ATP. Xestospongin C, an inositol 1,4,5-trisphosphate (IP3) receptor blocker, attenuated STOCs, but these events were not affected by ryanodine. The data suggest that purinergic activation through P(2Y) receptors results in localized Ca2+ release via PLC- and IP3-dependent mechanisms. Release of Ca2+ is coupled to STOCs, which are composed of currents mediated by large-conductance Ca2+- activated K+ channels and SK channels. The latter are thought to mediate hyperpolarization and relaxation responses of gastrointestinal muscles to inhibitory purinergic stimulation.

Original languageEnglish
Pages (from-to)C352-C362
JournalAmerican Journal of Physiology - Cell Physiology
Volume278
Issue number2 47-2
DOIs
Publication statusPublished - 2000 Jan 1

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

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