BrainPharm citations
Presenilin 1 deficiency alters the activity of voltage-gated Ca2+ channels in cultured cortical neurons
Cook DG, Li X, Cherry SD, Cantrell AR.
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. In addition, chelating intracellular Ca(2+) with 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) produced an increase in Ca(2+) current amplitude that was comparable to the increase caused by PS1 deficiency. In contrast to this, BAPTA had no effect on voltage-dependent Ca(2+) conductances in PS1-deficient neurons. These data suggest that PS1 deficiency may influence voltage-gated Ca(2+) channel function by means that involve intracellular Ca(2+) signaling. These findings reveal that PS1 functions at multiple levels to regulate and stabilize intracellular Ca(2+) levels that ultimately control neuronal firing behavior and influence synaptic transmission.
Other categories referring to 16148264
Pathological mechanism.Citation   (1)
Revisions: 3
Last Time: 7/25/2006 1:23:10 PM
Reviewer: Tom Morse
Owner: Tom Morse