Calbindin-D28k fails to protect hippocampal neurons against ischemia in spite of its cytoplasmic calcium buffering properties: evidence from calbindin-D28k knockout mice

Neuroscience. 1998 Jul;85(2):361-73. doi: 10.1016/s0306-4522(97)00632-5.


Cytoplasmic calcium-binding proteins are thought to shield neurons against damage induced by excessive Ca2+ elevations. Yet, in theory, a mobile cellular Ca2+ buffer could just as well promote neuronal injury by facilitating the rapid dispersion of Ca2+ throughout the cytoplasm. In sharp contrast to controls, in mice lacking the gene for calbindin-D28k, synaptic responses of hippocampal CA1 pyramidal neurons which are normally extremely vulnerable to ischemia, recovered significantly faster and more completely after a transient oxygen-glucose deprivation in vitro, and sustained less cellular damage following a 12 min carotid artery occlusion in vivo. Other cellular and synaptic properties such as the altered adaptation of action potential firing, and altered paired-pulse and frequency potentiation at affected synapses in calbindin-D28k-deficient mice were consistent with a missing intraneuronal Ca2+ buffer. Our findings provide direct experimental evidence against a neuroprotective role for calbindin-D28k.

Publication types

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

MeSH terms

  • Animals
  • Brain Ischemia / metabolism
  • Brain Ischemia / prevention & control*
  • Buffers
  • Calbindin 1
  • Calbindins
  • Calcium / metabolism*
  • Cytoplasm / metabolism
  • Glucose / deficiency
  • Hippocampus / blood supply
  • Hippocampus / drug effects
  • Hippocampus / pathology*
  • In Vitro Techniques
  • Ion Channels / drug effects
  • Ion Channels / metabolism
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • N-Methylaspartate / metabolism
  • Nerve Tissue Proteins / pharmacology*
  • Oxygen / metabolism
  • S100 Calcium Binding Protein G / pharmacology*


  • Buffers
  • Calb1 protein, mouse
  • Calbindin 1
  • Calbindins
  • Ion Channels
  • Nerve Tissue Proteins
  • S100 Calcium Binding Protein G
  • N-Methylaspartate
  • Glucose
  • Oxygen
  • Calcium