Ma. Noguera et al., CHARACTERIZATION OF 2 DIFFERENT CA2+ ENTRY PATHWAYS DEPENDENT ON DEPLETION OF INTERNAL CA2+ POOLS IN RAT AORTA, Naunyn-Schmiedeberg's archives of pharmacology, 357(2), 1998, pp. 92-99
Ryanodine (10 mu M), thapsigargin (1 mu M) and cyclopiazonic acid (10
mu M) produced a slow, sustained contractile response in rat aorta tha
t only can be observed in Ca2+-containing solution. In Ca2+-free mediu
m, no response to the drugs was obtained, which suggests that the cont
raction elicited in presence of Ca2+ is mainly due to the contribution
of extracellular influx. This Ca2+ entry does not depend on the openi
ng of dihydropyridine-dependent Ca2+-channels for nimodipine does not
affect this. Noradrenaline (1 mu M) induced a biphasic response in Ca2
+-free medium that was mediated by two different Ca2+ compartments, on
e of-which is common to caffeine (10 mM), and is also depleted by ryan
odine (10 mu M), thapsigargin (1 mu M) and cyclopiazonic acid(10 mu M)
This compartment loses its Ca2+ content after long exposure (65 min)
to Ca2+-free EDTA-containing solution and its refilling was also affec
ted by the three agents tested. The other compartment depleted by nora
drenaline, but not by caffeine, was also insensitive to ryanodine, tha
psigargin and cyclopiazonic acid, and did not lose its Ca2+ after 65 m
in in Ca2+-free medium. Contractions induced by noradrenaline (1 mu M)
or caffeine (10 mM) in Ca2+-free medium were not affected by ryanodin
e, thapsigargin and cyclopiazonic acid when these agents were added 1
min before or during the response to each agonist. After depletion of
internal Ca2+ stores sensitive to noradrenaline, an increase in the re
sting tone (IRT) of rat aorta was observed when Ca2+ was added again i
n absence of the agonist. This IRT was not affected by treatment with
ryanodine, thapsigargin and cyclopiazonic acid, and represents a Ca2entry pathway dependent on the depletion of the noradrenaline-sensitiv
e Ca2+ compartment. In conclusion, we can differentiate two Ca2+ entry
pathways in rat aorta that depend on the previous depletion of two in
ternal Ca2+ compartments: One corresponds to the classic capacitative
Ca2+ entry model and is promoted by depletion of the internal pool sen
sitive to noradreanline, caffeine, ryanodine, thapsigargin and cyclopi
azonic acid, the other is dependent only on depletion of an alpha(1)-a
drenoceptor-sensitive Ca2+ pool.