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AIM:To explore the role of prostaglandin F2α(PGF2α) on pacemaker activity in interstitial cells of Cajal(ICC)from mouse small intestine. METHODS:In this study,effects of PGF2αin the cultured ICC cells were investigated with patch clamp technology combined with Ca 2+ image analysis. RESULTS:Externally applied PGF2α(10μmol/L)produced membrane depolarization in current-clamp mode and increased tonic inward pacemaker currents in voltage-clamp mode.The application of flufenamic acid(a non-selective cation channel inhibitor)or niflumic acid(aCl channel inhibitor)abolished the generation of pacemaker currents but only flufenamic acid inhibited the PGF2α-induced tonic inward currents.In addition,the tonic inward currents induced by PGF2αwere not inhibited by intracellular application of 5’-[-thio]diphosphate trilithium salt.Pretreatment with Ca 2+ free solution, U-73122,an active phospholipase C inhibitor,and thapsigargin,a Ca 2+ -ATPase inhibitor in endoplasmic reticulum,abolished the generation of pacemaker currents and suppressed the PGF2α-induced tonic inward currents.However,chelerythrine or calphostin C,protein kinase C inhibitors,did not block the PGF2α-induced effects on pacemaker currents.When recording intracellular Ca 2+ ([Ca 2+ ]i)concentration using fluo-3/AM,PGF2α broadly increased the spontaneous[Ca 2+ ]i oscillations. CONCLUSION:These results suggest that PGF2αcan modulate pacemaker activity of ICC by acting non-selective action channels through phospholipase C-dependent pathway via[Ca2+]i regulation
AIM: To explore the role of prostaglandin F2α (PGF2α) on pacemaker activity in interstitial cells of Cajal (ICC) from mouse small intestine. METHODS: In this study, effects of PGF2αin the cultured ICC cells were investigated with patch clamp technology combined with Ca 2+ image analysis. RESULTS: Externally applied PGF2α (10 μmol / L) produced membrane depolarization in current-clamp mode and increased tonic inward pacemaker currents in voltage-clamp mode. The application of flufenamic acid (a non-selective cation channel inhibitor) or niflumic acid (aCl channel inhibitor) abolished the generation of pacemaker currents but only flufenamic acid inhibited the PGF2α-induced tonic inward currents. In addition, the tonic inward currents induced by PGF2 alpha not inhibited by intracellular application of 5 ’- [- thio] diphosphate trilithium salt. Treatment with Ca 2+ free solution, U-73122, an active phospholipase C inhibitor, and thapsigargin, a Ca 2+ -ATPase inhibitor in endoplasmic reticulum, abolished th e generation of pacemaker currents and suppressed the PGF2α-induced tonic inward currents. Yet, chelerythrine or calphostin C, protein kinase C inhibitors, did not block the PGF2α-induced effects on pacemaker currents. When recording intracellular Ca 2+ ([Ca 2+ ] i) concentration using fluo-3 / AM, PGF2α broadly increased the spontaneous [Ca 2+] i oscillations. CONCLUSION: These results suggest that PGF2αcan modulate pacemaker activity of ICC by acting non-selective action channels through phospholipase C-dependent pathway via [Ca2 +] i regulation