Pg. Wood et Ji. Gillespie, IN PERMEABILIZED ENDOTHELIAL-CELLS IP3-INDUCED CA2+ RELEASE IS DEPENDENT ON THE CYTOPLASMIC CONCENTRATION OF MONOVALENT CATIONS, Cardiovascular Research, 37(1), 1998, pp. 263-270
Objective: IP3-induced Ca2+ release from the intracellular stores play
s a role in the production of vasoactive substances in the endothelium
. In many cells, Ca2+ release is accompanied by an inward movement of
K+ whose function may be to dissipate the potential difference created
by the loss of positive charge from the internal stores. The existenc
e of such a mechanism in endothelial cells was investigated. Methods:
Using saponin-permeabilised bovine aortic endothelial (BAE) cells, the
effects of K+ on the IP3-induced Ca-45(2+) release were investigated.
Results: Replacement of K+ with NMG inhibited IP3 (3 mu M)-induced Ca
-45(2+) release by 55%. The ability of other ions to allow IP3-induced
Ca-45(2+) release was found to be K+ = Na+ > Cs+ > Rb+ much greater t
han Co2+. The K+ channel blockers TEA, 4AP and 3,4-DAP were found to s
ignificantly inhibit IP3-induced Ca-45(2+) release by 16%, 36%! and 27
%, respectively. Conclusions: The data suggest that Ca2+ release from
intracellular stores is partly dependent on a movement of K+ through K
+ channels in the store membranes. In contrast, 9AA (400 mu M) and sub
stitution with Co2+ abolished the response. Therefore, K+ is important
for IP3-induced Ca-45(2+) release, but other ions are also likely to
act as counter-ions. 9AA and Co2+ probably act on sites other than tho
se involving ER monovalent cation channels. The possibility that a cou
nter-ion system plays a role in the activation of endothelial cells is
discussed. (C) 1998 Elsevier Science B.V.