Incubation of nerve endings with a physiological concentration of Aβ1-42 activates CaV2.2(N-Type)-voltage operated calcium channels and acutely increases glutamate and noradrenaline release
Affiliations: [a] Department of Chemistry, Texas Christian University, Fort Worth, TX, 76129, USA | [b] Department of Community and Environmental Medicine, University of California, Irvine, CA, 92697, USA
Correspondence:
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Corresponding author: Joseph A. Bobich, Chemistry Department, T.C.U. Box 298860, Fort Worth, TX 76129, USA. Tel.: +1 817 257 6199; Fax: +1 817 257 5851; E-mail: [email protected].
Abstract: We wish to understand the normal function of amyloid-β peptides (Aβ) and to see if they destabilize neuronal calcium homeostasis [Mattson et al., J. Neurosci. 12 (1992), 376–389]. We observed that a physiological concentration (10 nM) of Aβ1-42 increased both glutamate and noradrenaline exocytosis from rat cortical nerve endings at least in part by activation of N-type Ca2+ channels. Aβ oligomers rather than monomers or fibrils probably are the most active form. Three alternatively-proposed effects of Aβ (reactive oxygen species formation, membrane perforation, and disruption of Ca2+ stores) also were tested by incubating nerve endings with a relatively high (by this study's standards) concentration of Aβ1-42 (100 nM). None of the three proposed effects were detected during these incubations. These results support the hypothesis that persistent elevations of Aβ, which normally operates as a modulator of N-type voltage gated calcium channels, could increase internal nerve ending Ca2+ and excitatory neurotransmitter release to produce the early neurotoxic effects that eventually lead to Alzheimer's disease.
