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8986775
Effect of beta-amyloid block of the fast-inactivating K+ channel on intracellular Ca2+ and excitability in a modeled neuron.
Good TA, Murphy RM
beta-Amyloid peptide (A beta), one of the primary protein components of senile plaques found in Alzheimer disease, is believed to be toxic to neurons by a mechanism that may involve loss of intracellular calcium regulation. We have previously shown that A beta blocks the fast-inactivating potassium (A) current. In this work, we show, through the use of a mathematical model, that the A beta-mediated block of the A current could result in increased intracellular calcium levels and increased membrane excitability, both of which have been observed in vitro upon acute exposure to A beta. Simulation results are compared with experimental data from the literature; the simulations quantitatively capture the observed concentration dependence of the neuronal response and the level of increase in intracellular calcium.
93
15130-5
1996
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Pathological mechanism.Citation   (1)
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