DOMINANT ROLE OF MITOCHONDRIA IN CLEARANCE OF LARGE CA2+ LOADS FROM RAT ADRENAL CHROMAFFIN CELLS

Cytosolic Ca2+ (Ca-c(2+)) clearance from adrenal chromaffin cells was studied by whole-cell patch clamp and indo-1 Ca2+ photometry after inf lux of Ca2+ through voltage-dependent Ca2+ channels. We isolated the r ates of Ca-c(2+) clearance by several mechanisms using combinations of the following agents (with their expected targets): Li+ or TEA substi tuted for Na+ (Na+-Ca2+ exchange), 1 mM La3+ applied after the depolar ization (Na+-Ca2+ exchange and plasma membrane Ca2+-ATPase), 1 mu M th apsigargin (pumping into reticular stores), and 2 mu M carbonyl cyanid e m-chlorophenylhydrazone (uptake into mitochondria). Remarkably, when ever [Ca2+](c) rose above similar to 500 nM, Ca-c(2+) clearance by mit ochondria exceeded clearance by either Na+-Ca2+ exchange or the Ca2+ p umps of the plasma and reticular membranes. As [Ca2+](c) fell again, C a2+ re-emerged from mitochondria, prolonging the final return to basal levels.