Involvement of Thromboxane A<SUB>2</SUB> in the Modulation of Pacemaker Activity of Interstitial Cells of Cajal of Mouse Intestine

Involvement of Thromboxane A<SUB>2</SUB> in the Modulation of Pacemaker Activity of Interstitial Cells of Cajal of Mouse Intestine

Although many studies show that thromboxane A₂ (TXA₂) has the action of gastrointestinal (GI) motility using GI muscle cells and tissue, there are no reports on the effects of TXA₂ on interstitial cells of Cajal (ICC) that function as pacemaker cells in GI tract. So, we studied the modulation of pacemaker activities by TXA₂ in ICC with whole cell patch-clamp technique. Externally applied TXA₂ (5&#1356;M) produced membrane depolarization in current-clamp mode and increased tonic inward pacemaker currents in voltage-clamp mode. The tonic inward currents by TXA₂ were inhibited by intracellular application of GDP-&#1346;-S. The pretreatment of ICC with Ca²⁺ free solution and thapsigargin, a Ca²⁺-ATPase inhibitor in endoplasmic reticulum, abolished the generation of pacemaker currents and suppressed the TXA₂-induced tonic inward currents. However, chelerythrine or calphostin C, protein kinase C inhibitors, did not block the TXA₂-induced effects on pacemaker currents. These results suggest that TXA₂ can regulate intestinal motility through the modulation of ICC pacemaker activities. This modulation of pacemaker activities by TXA₂ may occur by the activation of G protein and PKC independent pathway via extra and intracellular Ca²⁺ modulation.