Pathological mechanism

Data

Name Presenilin-1 deficient neurons have increased activity of L channels

Description

Hypothesis Dendritic Hypothesis - Ca++ currents Show Other

Extracelular pathological element

Intracelular pathological element Presenilin-1 Show Other

Pathological action Reduces Show Other

Process

Process action

Transmitter(s)

Receptor(s)

Channel(s) I L high threshold Show Other

Pharmacological Agent

Pharmacological Action

Brain region

Neuron

Cell model Cultured cortical neurons Show Other

Cellular compartment

PubMed ID 16148264

Citation Presenilin 1 deficiency alters the activity of voltage-gated Ca2+ channels in cultured cortical neurons Show Other

AlzWeb

Notes Presenilins 1 and 2 (PS1 and PS2, respectively) play a critical role in mediating gamma-secretase cleavage of the amyloid precursor protein (APP). Numerous mutations in the presenilins are known to cause early-onset familial Alzheimer's disease (FAD). In addition, it is well established that PS1 deficiency leads to altered intracellular Ca(2+) homeostasis involving endoplasmic reticulum Ca(2+) stores. However, there has been little evidence suggesting Ca(2+) signals from extracellular sources are influenced by PS1. Here we report that the Ca(2+) currents carried by voltage-dependent Ca(2+) channels are increased in PS1-deficient cortical neurons. This increase is mediated by a significant increase in the contributions of L- and P-type Ca(2+) channels to the total voltage-mediated Ca(2+) conductance in PS1 (-/-) neurons. (Cook et al. 2005)

Pathology Alzheimer Show Other

Stage

Question

Claim Aß causes increased Ca++ influx by activation of L-type Ca++ channels Show Other