Recent studies indicate that the Ca2+ permeability of the sarcoplasmic reti
culum (SR) can be affected by its anionic environment. Additionally, anions
could directly modulate the SR Ca2+ pump or the movement of compensatory c
harge across the SR membrane during Ca2+ uptake or release. To examine the
effect of anion substitution on cardiac SR Ca2+ uptake, fluorometric Ca2+ m
easurements and spectrophotometric ATPase assays were used. Ca2+ uptake int
o SR vesicles was inhibited in a concentration-dependent manner when Br- or
I- replaced extravesicular Cl- (when Br- completely replaced Cl-, uptake v
elocity was; 70% of control; when I- completely replaced Cl-, uptake veloci
ty was similar to 39% of control). Replacement of Cl- with SO42- had no eff
ect on SR uptake. Although both I- and Br- inhibited net Ca2+ uptake, neith
er anion directly inhibited the SR Ca2+ pump nor did they increase the perm
eability of the SR membrane to Ca2+. Our results support the hypothesis tha
t an anionic current that occurs during SR Ca2+ uptake is reduced by the su
bstitution of Br- or I- for Cl-.