Dc. Batlle et al., CYTOSOLIC FREE CALCIUM REGULATION IN RESPONSE TO ACUTE CHANGES IN INTRACELLULAR PH IN VASCULAR SMOOTH-MUSCLE, The American journal of physiology, 264(4), 1993, pp. 932-943
This study examined the mechanisms whereby alterations of intracellula
r pH (pH(i)) impact on free cytosolic calcium (Ca(i)2+) in cultured ra
t aortic vascular smooth muscle cells (VSMC) assayed in the presence o
f HCO3/CO2. Rapid cell alkalinization, effected by the exposure to NH4
Cl or removal Of CO2 from the superfusate, produced a rapid increase i
n Ca2+. The rise in Ca2+ was markedly diminished when sarcoplasmic ret
iculum (SR) Ca2+ stores had been depleted by prior exposure to arginin
e vasopressin (AVP) in Ca2+-free media or when SR release and reuptake
of Ca2+ were blocked by the addition of 3,4,5-trimethoxybenzoic acid
8-(diethylamino)octyl ester (TMB-8), but was unaffected by the removal
of external Ca2+ or inhibition of Ca2+ entry using NiCl2. Cell acidif
ication also resulted in a rapid increase in Ca(i)2+. This Ca2+ increa
se was most apparent when pH(i) was very low (<6.6) and was unaffected
by removal of external Ca2+ or NiCl2 addition. Unlike the effect of c
ell alkalinization, the increase in Ca2+ associated with cell acidific
ation was not prevented by pretreatment with AVP or TMB-8. We conclude
that, in cultured VSMC, acute intracellular alkalinization and, to a
lesser extent, acidification result in release of Ca2+ from internal s
tores. Alkalinization increases Ca(i)2+ by promoting its release from
a store which is AVP and TMB-8 sensitive, most likely the SR. Cell aci
dification increases Ca(i)2+ from an intracellular store(s) that is ne
ither AVP nor TMB-8 sensitive. The increase in Ca2+ produced by cell a
cidification may be explained on the basis of cell buffering such that
, as cytosolic H+ increases, it displaces Ca(i)2+ from internal buffer
s with similar affinities for Ca2+ and H+.