Dominant role of mitochondria in clearance of large Ca2+ loads from rat adrenal chromaffin cells.
Cytosolic Ca2+ (Ca2+c) clearance from adrenal chromaffin cells was studied by whole-cell patch clamp and indo-1 Ca2+ photometry after influx of Ca2+ through voltage-dependent Ca2+ channels. We isolated the rates of Ca2+c clearance by several mechanisms using combinations of the following agents (with their expected targets): Li+ or TEA substituted for Na+ (Na(+)-Ca2+ exchange), 1 mM La3+ applied after the depolarization (Na(+)-Ca2+ exchange and plasma membrane Ca(2+)-ATPase), 1 microM thapsigargin (pumping into reticular stores), and 2 microM carbonyl cyanide m-chlorophenylhydrazone (uptake into mitochondria). Remarkably, whenever [Ca2+]c rose above approximately 500 nM, Ca2+c clearance by mitochondria exceeded clearance by either Na(+)-Ca2+ exchange or the Ca2+ pumps of the plasma and reticular membranes. As [Ca2+]c fell again, Ca2+ reemerged from mitochondria, prolonging the final return to basal levels.
Herrington
J
J
Department of Physiology and Biophysics, University of Washington, Seattle 98195-7290, USA.
Park
Y B
YB
Babcock
D F
DF
Hille
B
B
D000313:Adrenal Medulla / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019070:Cell Lineage; D002478:Cells, Cultured; D007424:Intracellular Fluid / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D007811:Lanthanum / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology*; D009432:Neural Crest; D009474:Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger; D013729:Terpenes / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D019284:Thapsigargin
D002121:Calcium Channel Blockers; D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D013729:Terpenes; D013757:Tetraethylammonium Compounds; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D019789:Tetraethylammonium; D019284:Thapsigargin; D007811:Lanthanum; D008094:Lithium; D000252:Calcium-Transporting ATPases; D002118:Calcium