CALBINDIN-D-28K FAILS TO PROTECT HIPPOCAMPAL-NEURONS AGAINST ISCHEMIAIN SPITE OF ITS CYTOPLASMIC CALCIUM BUFFERING PROPERTIES - EVIDENCE FROM CALBINDIN-D-28K KNOCKOUT MICE

Cytoplasmic calcium-binding proteins are thought to shield neurons aga inst damage induced by excessive Ca2+ elevations. Yet, in theory, a mo bile cellular Ca2+ buffer could just as well promote neuronal injury b y facilitating the rapid dispersion of Ca2+ throughout the cytoplasm. In sharp contrast to controls, in mice lacking the gene for calbindin- D-28k, synaptic responses of hippocampal CA1 pyramidal neurons which a re normally extremely vulnerable to ischemia, recovered significantly faster and more completely after a transient oxygen-glucose deprivatio n in vitro, and sustained less cellular damage following a 12 min caro tid artery occlusion iii 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 calbi ndin-D-28k-deficient mice were consistent with a missing intraneuronal Ca2+ buffer. Our findings provide direct experimental evidence agains t a neuroprotective role for calbindin-D-28k. (C) 1998 IBRO. Published by Elsevier Science Ltd.