Principle investigator: Ulrich Schröder ( )

A characteristic feature of cerebral ischemia is the loss of the intracellular ion homeostasis. An excessive increase in intracellular calcium (Ca2+)i as well as of sodium ions (Na+)i, and a significant loss of intracellular potassium ions (K+)i lead to an excessive release of neurotransmitters like glutamate and GABA and, in the end, to cell death. We examine which ion transporters and ion channels contribute in which time window to the neuronal damage in vivo and in vitro. We are also interested in how the distribution of the isoforms of different transport systems changes after cerebral ischemia,

At the moment we deal with the following questions:

1. distribution of the Na+-K+-2Cl- -co-transporter, whose inhibition was shown to be protective in vitro (Busse et al., in 2005), before and after ischemia in vivo
2. role of the different isoforms of the Na+/H+ exchangers in ischemia
3. impact of K+- channels on ischemic damage

We showed that

1. the distribution of the Na+-K+-2Cl- -co-transporter differs in the different brain regions
2. the inhibition of the Na+/H+ by broad spectrum inhibitors is neuroprotective
   
3. the activators of the ATP-regulated K+- channels decrease the ischemia-induced damage in the hippocampus

Different ion transport systems share the driving forces provided by the different ion gradients

In area CA1 of the rat hippocampus the Na+-K+-2Cl- co-transporter is mainly localized on the cell bodies of the neurons

Harmaline, a broad spectrum inhibitor of Na+/H+ exchangers, protects hippocampal neurons even after an ischemic insult