| First Author | Cook DG | Year | 2005 |
| Journal | J Neurophysiol | Volume | 94 |
| Issue | 6 | Pages | 4421-9 |
| PubMed ID | 16148264 | Mgi Jnum | J:116810 |
| Mgi Id | MGI:3695065 | Doi | 10.1152/jn.00745.2005 |
| Citation | Cook DG, et al. (2005) Presenilin 1 deficiency alters the activity of voltage-gated Ca2+ channels in cultured cortical neurons. J Neurophysiol 94(6):4421-9 |
| abstractText | 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. |
