QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, April 9, 2008, 28(15):3877-3886; doi:10.1523/JNEUROSCI.0675-08.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Powell, A. D. Articles by Jefferys, J. G. R. PubMed PubMed Citation Articles by Powell, A. D. Articles by Jefferys, J. G. R.

 Previous Article  |  Next Article 

Cellular/Molecular
Alterations in Ca²⁺-Buffering in Prion-Null Mice: Association with Reduced Afterhyperpolarizations in CA1 Hippocampal Neurons

Andrew D. Powell,¹ Emil C. Toescu,² John Collinge,³ and John G. R. Jefferys¹

Divisions of ¹Neuroscience (Neurophysiology) and ²Medical Sciences (Physiology), The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom, and ³Medical Research Center Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom

Correspondence should be addressed to John G. R. Jefferys at the above address. Email: J.G.R.Jefferys{at}bham.ac.uk

Prion protein (PrP) is a normal component of neurons, which confers susceptibility to prion diseases. Despite its evolutionary conservation, its normal function remains controversial. PrP-deficient (Prnp^0/0) mice have weaker afterhyperpolarizations (AHPs) in cerebellar and hippocampal neurons. Here we show that the AHP impairment in hippocampal CA1 pyramidal cells is selective for the slow AHP, and is not caused by an impairment of either voltage-gated Ca²⁺ channels or Ca²⁺-activated K⁺ channels. Instead, Prnp^0/0 neurons have twofold to threefold stronger Ca²⁺ buffering and double the Ca²⁺ extrusion rate. In Prnp^0/0 neurons thapsigargin abolished the stronger Ca²⁺ buffering and extrusion, and thapsigargin or cyclopiazonic acid abolished the weakening of the slow AHPs. These data implicate sarcoplasmic/endoplasmic reticulum calcium ATPase in the enhanced Ca²⁺ buffering, and extrusion into the endoplasmic reticulum, which contains substantial amounts of PrP in wild-type mice. Altered Ca²⁺ homeostasis can explain several phenotypes identified in Prnp^0/0 mice.

Key words: calcium signaling; endoplasmic reticulum; AHP; hippocampus; prion; transgenic

---

Received May 11, 2007; accepted Feb. 24, 2007.

Correspondence should be addressed to John G. R. Jefferys at the above address. Email: J.G.R.Jefferys{at}bham.ac.uk

Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2008 28: i. [Full Text]  

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help