Fig. 7.
Mechanisms underlying E2 effects on [Ca2+]i regulation in human ASM cells. A: pretreatment with the l-type Ca2+ channel inhibitor nifedipine (1 μM) blunted E2 effects on [Ca2+]i responses to histamine (n = 4), suggesting a partial role for this influx mechanism in E2 effects. B: however, pretreatment with the Ca2+-activated K+ channel inhibitor iberiotoxin did not considerably change E2 effects (but did increase the [Ca2+]i response to histamine as expected due to membrane depolarization; n = 4). C: using previously published protocols (1), assessment of store-operated Ca2+ entry (SOCE) showed that preexposure to E2 significantly decreased the extent of Ca2+ influx by this mechanism [n = 4; cyclopiazonic acid (CPA), inhibitor of sarcoplasmic reticulum (SR) Ca2+ reuptake; see materials and methods for protocol details]. Pretreatment with the receptor-operated channel inhibitor SKF-96365 or the Na+-Ca2+ exchange inhibitor KB-R7943 slightly decreased Ca2+ influx as evaluated using the SOCE protocol. Nonetheless, even in the presence of either inhibitor, E2 significantly blunted Ca2+ influx, indicating a predominant effect on SOCE per se (n = 4). Values are means ± SE. *Significant effect of E2; #significant inhibitor effect (P < 0.05). Veh, vehicle.