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Role of ion channels and ion exchangers in cerebral ischemia
Prominent features of cerebral ischemia are the strong depolarisation of neuronal and glial membranes, the excessive intracellular accumulation of both calcium (Ca 2+ ) i and sodium (Na + ) i , and a major loss of intracellular potassium (K + ) i . The final outcome of these ion movements is an excessive release of neurotransmitters such as glutamate and GABA and subsequently cell death. While the involvement of ligand-gated ion channels, Ca 2+ channels and Na + channels has been extensively investigated, the other ion channels and the ion exchangers have received little attention. Ion exchangers and co-transporters are coupled to the ion gradients across the cell membrane, are interdependent ( Fig.1 ) and are important for cellular ion, pH and volume homeostasis and for the uptake of substrates. We investigate whether, how and in which time window these transporters affect ischemic neuronal damage .
Influence of K-ATP channels on ischemic damage
ATP-regulated potassium channels (K-ATP channels) have become an attractive target of investigation in the pathophysiology of neurodegeneration. To date it is believed that K-ATP channel openers can reduce ischemia-induced brain damage and that they have a preconditioning action that involves the mitochondria. Due to the limited availability of subtype-specific compounds which do not affect the mitochondrial K-ATP channels, however, this hypothesis has not yet been clearly proven. By utilizing new drugs targeting specifically plasmalemmal K-ATP channels we want to clarify w h ether or not activation of those channels is sufficient to promote neuronal survival in cerebral hypoxia or ischaemia .
Principle investigator: Ulrich Schröder
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Breder J, Sabelhaus CF, Opitz T, Reymann KG, Schröder UH (2000) Inhibition of different pathways influencing Na+ homeostasis protects organotypic hippocampal slice cultures from hypoxic/hypoglycemic injury. Neuropharmacology 39:1779-1787
Schröder UH, Breder J, Sabelhaus CF, Reymann KG. (1999) The novel Na+/ Ca2+ exchange inhibitor KB-R7943 protects CA1 neurons in rat hippocampal slices against hypoxic/hypoglycemic injury. Neuropharmacology 38: 319-321