Capacitative Ca2+ entry is essential for refilling intracellular Ca2+ store
s and is thought to be regulated primarily by inositol 1, 4,5-trisphosphate
(IP3)-sensitive stores in nonexcitable cells, In nonexcitable A549 cells,
the application of caffeine or ryanodine induces Ca2+ release in the absenc
e of extracellular Ca2+ similar to that induced by thapsigargin (Tg), and C
a2+ entry occurs upon the readdition of extracellular Ca2+. The channels th
us activated are also permeable to Mn2+. The channels responsible for this
effect appear to be activated by the depletion of caffeine/ryanodine-sensit
ive stores per se, as evidenced by the activation even in the absence of in
creased intracellular Ca2+ concentration. Tg pretreatment abrogates the res
ponse to caffeine/ryanodine, whereas Tg application subsequent to caffeine/
ryanodine treatment induces further Ca2+ release. The response to caffeine/
ryanodine is also abolished by initial ATP application, whereas ATP added s
ubsequent to caffeine/ryanodine induces additional Ca2+ release. RT-PCR ana
lyses showed the expression of a type 1 ryanodine receptor, two human homol
ogues of transient receptor potential protein (hTrp1 and hTrp6), as well as
all three types of the IP3 receptor. These results suggest that in A549 ce
lls, (i) capacitative Ca2+ entry can also be regulated by caffeine/ryanodin
e-sensitive stores, and (ii) the RyR-gated stores interact functionally wit
h those sensitive to IP3, probably via Ca2+-induced Ca2+ release.