title: Intracellular calcium events activated by ATP in murine colonic myocytes.
abstract: ATP is a candidate enteric inhibitory neurotransmitter in visceral smooth muscles. ATP hyperpolarizes visceral muscles via activation of small-conductance, Ca(2+)-activated K(+) (SK) channels. Coupling between ATP stimulation and SK channels may be mediated by localized Ca(2+) release. Isolated myocytes of the murine colon produced spontaneous, localized Ca(2+) 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 Ca(2+) 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 Ca(2+) events in colonic myocytes "Ca(2+) puffs. " The P(2Y) receptor agonist 2-methylthio-ATP (2-MeS-ATP) increased the intensity and frequency of Ca(2+) puffs. 2-MeS-ATP also increased STOCs in association with the increase in Ca(2+) puffs. Pyridoxal-phospate-6-azophenyl-2',4'-disculfonic acid tetrasodium, a P(2) receptor inhibitor, blocked responses to 2-MeS-ATP. Spontaneous Ca(2+) transients and the effects of 2-MeS-ATP on Ca(2+) 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 IP(3) receptor-operated stores, ryanodine receptors may be recruited during agonist stimulation to amplify release of Ca(2+). These data suggest that localized Ca(2+) release modulates Ca(2+)-dependent ionic conductances in the plasma membrane. Localized Ca(2+) release may contribute to the electrical responses resulting from purinergic stimulation.
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA.
authors.forename: O
authors.initials: O
authors.lastname: Bayguinov
authors.forename: B
authors.initials: B
authors.lastname: Hagen
authors.forename: A D
authors.initials: AD
authors.lastname: Bonev
authors.forename: M T
authors.initials: MT
authors.lastname: Nelson
authors.forename: K M
authors.initials: KM
authors.lastname: Sanders
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004553:Electric Conductivity; D005260:Female; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D058910:Purinergic P2 Receptor Agonists; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D058910:Purinergic P2 Receptor Agonists; D013873:Thionucleotides; D000255:Adenosine Triphosphate; D002118:Calcium; C008501:2-methylthio-ATP