Acute Effects of β-Amyloid (1-42) Oligomers on Rat Pyramidal Entorhinal Neurons

Abstract

Deposition of beta-amyloid peptide (Aβ) in senile plaques is the hallmark of Alzheimer disease neuropathology. Soluble Aβ oligomers block voltage-gated ion channels as P/Q type calcium channels (Nimmrich et al., 2008) as well as the transient potassium current (Liudyno et al., 2012) and calcium dependent potassium channels, BK type (Yamamoto et al., 2011). Exposure to Aβ may cause a loss of cellular calcium homeostasis, but the mechanism by which this occurs is uncertain. In this work we evaluated the acute response of rat pyramidal entorhinal neurons to oligomers formed from purified Aβ1-42 in both entorhinal cortex slice preparations and isolated pyramidal neurons in culture using current- and voltage-clamp conditions. Exposure to Aβ oligomers but not monomers increased the input resistance and enlarged the action potential in the slice preparation, whereas in culture neurons produced a reversible inhibition of the inward potassium current generated by voltage ramps from −70 to 70 mV in symmetric potassium conditions. This current is generated by inward rectifier potassium channels as well as the leak potassium channels, it was blocked by barium, arachidonic acid, bupivacaine and extracellular pH acidification, suggesting that TASK type K2P channels are targets of the toxic effects of Aβ. Blockage of potassium channels by Aβ could lead to prolonged cell depolarization, thereby increasing calcium influx.Supported by CONACyT (324341) Mexico.