Intracellular calcium events activated by ATP in murine colonic myocytes

Orline Bayguinov, Brian Hagen, Adrian D. Bonev, Mark T. Nelson, Kenton M. Sanders

    Research output: Contribution to journalArticlepeer-review


    ATP is a candidate enteric inhibitory neurotransmitter in visceral smooth muscles. ATP hyperpolarizes visceral muscles via activation of small- conductance, Ca2+-activated K+ (SK) channels. Coupling between ATP stimulation and SK channels may be mediated by localized Ca2+ release. Isolated myocytes of the murine colon produced spontaneous, localized Ca2+ release events. These events corresponded to spontaneous transient outward currents (STOCs) consisting of charybdotoxin (ChTX)-sensitive and - insensitive events. ChTX-insensitive STOCs were inhibited by apamin. Localized Ca2+ transients were not blocked by ryanodine, but these events were reduced in magnitude and frequency by xestospongin C (Xe-C), a blocker of inositol 1,4,5-trisphosphate receptors. Thus we have termed the localized Ca2+ events in colonic myocytes 'Ca2+ puffs.' The P(2Y) receptor agonist 2-methylthio-ATP (2-MeS-ATP) increased the intensity and frequency of Ca2+ puffs. 2-MeS-ATP also increased STOCs in association with the increase in Ca2+ puffs. Pyridoxal-phospate-6-azophenyl-2',4'-disculfonic acid tetrasodium, a P2 receptor inhibitor, blocked responses to 2-MeS-ATP. Spontaneous Ca2+ transients and the effects of 2-MeS-ATP on Ca2+ puffs and STOCs were blocked by U-73122, an inhibitor of phospholipase C. Xe-C and ryanodine also blocked responses to 2-MeS-ATP, suggesting that, in addition to release from IP3 receptor-operated stores, ryanodine receptors may be recruited during agonist stimulation to amplify release of Ca2+. These data suggest that localized Ca2+ release modulates Ca2+-dependent ionic conductances in the plasma membrane. Localized Ca2+ release may contribute to the electrical responses resulting from purinergic stimulation.
    Original languageEnglish
    Pages (from-to)C126-C135
    JournalAmerican Journal of Physiology: Cell Physiology
    Issue number1
    Publication statusPublished - 2000


    • Calcium puffs
    • Enteric neurotransmission
    • Local calcium transients
    • P(2Y) receptors


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