Ullah, Ghanim Demuro, Angelo Parker, Ian E. Pearson, John Analyzing and Modeling the Kinetics of Amyloid Beta Pores Associated with Alzheimer’s Disease Pathology <div><p>Amyloid beta (Aβ) oligomers associated with Alzheimer’s disease (AD) form Ca<sup>2+</sup>-permeable plasma membrane pores, leading to a disruption of the otherwise well-controlled intracellular calcium (Ca<sup>2+</sup>) homeostasis. The resultant up-regulation of intracellular Ca<sup>2+</sup> concentration has detrimental implications for memory formation and cell survival. The gating kinetics and Ca<sup>2+</sup> permeability of Aβ pores are not well understood. We have used computational modeling in conjunction with the ability of optical patch-clamping for massively parallel imaging of Ca<sup>2+</sup> flux through thousands of pores in the cell membrane of <i>Xenopus</i> oocytes to elucidate the kinetic properties of Aβ pores. The fluorescence time-series data from individual pores were idealized and used to develop data-driven Markov chain models for the kinetics of the Aβ pore at different stages of its evolution. Our study provides the first demonstration of developing Markov chain models for ion channel gating that are driven by optical-patch clamp data with the advantage of experiments being performed under close to physiological conditions. Towards the end, we demonstrate the up-regulation of gating of various Ca<sup>2+</sup> release channels due to Aβ pores and show that the extent and spatial range of such up-regulation increases as Aβ pores with low open probability and Ca<sup>2+</sup> permeability transition into those with high open probability and Ca<sup>2+</sup> permeability.</p></div> ion channel gating;Markov chain models;memory formation;cell membrane;β pore;Amyloid Beta Pores Associated;Xenopus oocytes;permeability;β pores;gating kinetics;ad;cell survival 2015-09-08
    https://plos.figshare.com/articles/dataset/_Analyzing_and_Modeling_the_Kinetics_of_Amyloid_Beta_Pores_Associated_with_Alzheimer_8217_s_Disease_Pathology_/1537137
10.1371/journal.pone.0137357