Beta-amyloid peptide blocks the fast-inactivating K+ current in rat hippocampal neurons.

AUTOR(ES)

Good, T A

RESUMO

Deposition of beta-amyloid peptide (A beta) in senile plaques is a hallmark of Alzheimer disease neuropathology. Chronic exposure of neuronal cultures to synthetic A beta is directly toxic, or enhances neuronal susceptibility to excitotoxins. Exposure to A beta may cause a loss of cellular calcium homeostasis, but the mechanism by which this occurs is uncertain. In this work, the acute response of rat hippocampal neurons to applications of synthetic A beta was measured using whole-cell voltage-clamp techniques. Pulse application of A beta caused a reversible voltage-dependent decrease in membrane conductance. A beta selectively blocked the voltage-gated fast-inactivating K+ current, with an estimated KI < 10 microM. A beta also blocked the delayed rectifying current, but only at the highest concentration tested. The response was independent of aggregation state or peptide length. The dynamic response of the fast-inactivating current to a voltage jump was consistent with a model whereby A beta binds reversibly to closed channels and prevents their opening. Blockage of fast-inactivating K+ channels by A beta could lead to prolonged cell depolarization, thereby increasing Ca2+ influx.

Documentos Relacionados

• Effect of β-amyloid block of the fast-inactivating K+ channel on intracellular Ca2+ and excitability in a modeled neuron
• Apoptosis is induced by beta-amyloid in cultured central nervous system neurons.
• Sulphonylureas reduce the slowly inactivating D-type outward current in rat hippocampal neurons.
• A non-inactivating K+ current sensitive to muscarinic receptor activation in rat cultured cerebellar granule neurons.
• Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans.