BK channels are voltage- and
calcium-dependent potassium channels whose activation tends to reduce cellular excitability. In hippocampal pyramidal cells,
BK channels repolarize somatic action potentials, and recent immunogold and electrophysiological analyses have revealed a presynaptic pool of
BK channels that can regulate
glutamate release. Agents that modulate
BK channel activity would therefore be expected to affect cell excitability and
neurotransmitter release also under pathological conditions. We have investigated the role of BK
potassium channels in a model of
ischemia-induced nerve cell degeneration. Organotypical slice cultures of rat hippocampus were exposed to
oxygen and
glucose deprivation (OGD), and cell death was assessed by the
fluorescent dye propidium iodide. OGD induced cell death in the CA1 region and to a lesser extent in CA3. Treatment with the
BK channel blockers,
paxilline and
iberiotoxin, during and after OGD induced increased cell death in CA1 and CA3. Both
BK channel blockers also sensitized the relatively resistant granule cells in fascia dentata to OGD. The effect of
paxilline and
iberiotoxin was evident from 3 h after OGD, indicating a role of
BK channels early in the post-ischemic phase or during OGD itself. The
BK channel opener,
NS1619, turned out to be gliotoxic, and this effect was not counteracted by
paxilline and
iberiotoxin. Our data show that blockade of
BK channels aggravates OGD-induced cell damage and suggest that
BK channels act as a kind of 'emergency brake' during and/or after
ischemia. Accordingly, the
BK channel is a potential molecular target for neuroprotective
therapy in
stroke.