title: Calbindin-D28K (CaBP) levels and calcium currents in acutely dissociated epileptic neurons.
abstract: Nerve cells that lack the cytoplasmic Ca2+ binding protein Calbindin-D28K (CaBP) appear to be selectively vulnerable to Ca(2+)-related injury consistent with a postulated intraneuronal Ca(2+)-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 less than 0.001; ANOVA). The Ca(2+)-buffering role of CaBP was assessed in acutely dissociated control and kindled GCs by examining a physiological process highly sensitive to intracellular Ca(2+)-buffering: the Ca(2+)-dependent inactivation of high-voltage activated (HVA or L-type) Ca2+ currents in the absence (or presence) of exogenous Ca(2+)-chelators. Whole-cell patch clamp recordings in kindled GCs demonstrated a markedly enhanced Ca(2+)-dependent inactivation of Ca(2+)-currents. After brief conditioning Ca2+ currents, in the absence of an exogenous intraneuronal Ca(2+)-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 less than 0.005; ANOVA). The differential Ca2+ current decay and Ca(2+)-dependent inactivation were prevented in both control and kindled GCs upon loading the neurons with the exogenous Ca(2+)-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 Ca(2+)-buffering in mammalian neurons.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University Medical Center, CA 94305.
authors.forename: G
authors.initials: G
authors.lastname: Köhr
authors.forename: C E
authors.initials: CE
authors.lastname: Lambert
authors.forename: I
authors.initials: I
authors.lastname: Mody
mesh_terms: D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D015220:Calcium Channels / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004827:Epilepsy / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007696:Kindling, Neurologic / Q000502:physiology; D008297:Male; D009474:Neurons / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D064030:S100 Calcium Binding Protein G / Q000032:analysis* / Q000276:immunology
chemical_list: C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D015220:Calcium Channels; D064030:S100 Calcium Binding Protein G; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid