Dominant role of mitochondria in clearance of large Ca2+ loads from rat adrenal chromaffin cells

Neuron. 1996 Jan;16(1):219-28. doi: 10.1016/s0896-6273(00)80038-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Medulla / cytology
  • Adrenal Medulla / embryology
  • Adrenal Medulla / metabolism*
  • Animals
  • Biological Transport / drug effects
  • Biological Transport, Active / drug effects
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium-Transporting ATPases / antagonists & inhibitors
  • Calcium-Transporting ATPases / metabolism*
  • Carbonyl Cyanide m-Chlorophenyl Hydrazone / pharmacology
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / metabolism*
  • Cell Lineage
  • Cells, Cultured
  • Intracellular Fluid / metabolism
  • Intracellular Membranes / drug effects
  • Intracellular Membranes / metabolism
  • Lanthanum / pharmacology
  • Lithium / pharmacology
  • Male
  • Membrane Potentials / drug effects
  • Mitochondria / physiology*
  • Neural Crest
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Calcium Exchanger
  • Terpenes / pharmacology
  • Tetraethylammonium
  • Tetraethylammonium Compounds / pharmacology
  • Thapsigargin

Substances

  • Calcium Channel Blockers
  • Carrier Proteins
  • Sodium-Calcium Exchanger
  • Terpenes
  • Tetraethylammonium Compounds
  • Carbonyl Cyanide m-Chlorophenyl Hydrazone
  • Tetraethylammonium
  • Thapsigargin
  • Lanthanum
  • Lithium
  • Calcium-Transporting ATPases
  • Calcium