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Calbindin-D28K (CaBP) levels and calcium currents in acutely dissociated epileptic neurons

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Nerve cells that lack the cytoplasmic Ca2+ binding protein Calbindin-D28K (CaBP) appear to be selectively vulnerable to Ca2+-related injury consistent with a postulated intraneuronal Ca2+-buffering role of CaBP. We have confirmed the selective loss of CaBP from the dentate gyrus during kindling-induced epilepsy in acutely dissociated granule cells (GCs) from kindled rats. Immunohistochemically stained kindled neurons showed a significant loss of CaBP when compared to controls (p < 0.001; ANOVA). The Ca2+-buffering role of CaBP was assessed in acutely dissociated control and kindled GCs by examining a physiological process highly sensitive to intracellular Ca2+-buffering: the Ca2+ -dependent inactivation of high-voltage activated (HVA or L-type) Ca2+ currents in the absence (or presence) of exogenous Ca2+-chelators. Whole-cell patch clamp recordings in kindled GCs demonstrated a markedly enhanced Ca2+-dependent inactivation of Ca2+-currents. After brief conditioning Ca2+ currents, in the absence of an exogenous intraneuronal Ca2+-chelator, subsequent test Ca2+ currents were inactivated by 58.3% in kindled GCs, a significant increase from the 37.4% inactivation observed in control GCs (p< 0.005; ANOVA). The differential Ca2+ current decay and Ca2+-dependent inactivation were prevented in both control and kindled GCs upon loading the neurons with the exogenous Ca2+-chelator BAPTA. These experiments demonstrate a high correlation between the loss of CaBP and changes in Ca2+ current inactivation and are consistent with the hypothesis that CaBP contributes to the physiological Ca2+-buffering in mammalian neurons.

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Correspondence to I. Mody.

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Köhr, G., Lambert, C.E. & Mody, I. Calbindin-D28K (CaBP) levels and calcium currents in acutely dissociated epileptic neurons. Exp Brain Res 85, 543–551 (1991). https://doi.org/10.1007/BF00231738

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Key words

  • Voltage-dependent Ca2+-currents (HVA or L-type)
  • Inactivation
  • Intraneuronal Ca2+
  • Buffering
  • Dentate gyrus granule cells
  • Kindling-induced epilepsy
  • Rat