CAPACITATIVE CA2+ ENTRY IN ENTERIC GLIA INDUCED BY THAPSIGARGIN AND EXTRACELLULAR ATP

Mobilization of intracellular Ca2+ stores is coupled to Ca2+ influx ac ross the plasma membrane, a process termed capacitative Ca2+ entry. Ca pacitative Ca2+ entry was examined in cultured guinea pig enteric glia exposed to 100 mu M ATP, an inositol trisphosphate-mediated Ca2+-mobi lizing agonist, and to 1 mu M thapsigargin, an inhibitor of microsomal Ca2+ ATPase. Both agents caused mobilization of intracellular Ca2+ st ores followed by influx of extracellular Ca2+. This capacitative Ca2influx was inhibited by Ni2+ (88 +/- 1%) and by La3+ (87 +/- 1%) but w as not affected by L- or N-type Ca2+ channel blockers. Pretreatment of glia with 100 nM phorbol 12-myristate 13-acetate for 24 h decreased c apacitative Ca2+ entry by 48 +/- 2%. Chelerythrine (0.1-10 mu M), a sp ecific antagonist of protein kinase C (PKC), dose dependently inhibite d capacitative Ca2+ entry. The nitric oxide synthase inhibitor N-G-nit ro-L-arginine (1 mM) decreased Ca2+ influx by 42 +/- 1%. Capacitative Ca2+ entry was inhibited to a similar degree by the guanylate cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one). Capacitative Ca2+ entry occurs in enteric glial cells via lanthanuminhibitable chan nels through a process regulated by PKC and nitric oxide.