Alterations in Ca2+-buffering in prion-null mice: Association with reduced afterhyperpolarizations in CA1 hippocampal neurons

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@article{bcddf9781f7b49dd84a31390a736de1d,
title = "Alterations in Ca2+-buffering in prion-null mice: Association with reduced afterhyperpolarizations in CA1 hippocampal neurons",
abstract = "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.",
keywords = "prion, transgenic, endoplasmic reticulum, hippocampus, calcium signaling, AHP",
author = "Andrew Powell and Emil Toescu and J Collinge and John Jefferys",
year = "2008",
month = jan,
day = "1",
doi = "10.1523/JNEUROSCI.0675-08.2008",
language = "English",
volume = "28",
pages = "3877--3886",
journal = "The Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "15",

}

RIS

TY - JOUR

T1 - Alterations in Ca2+-buffering in prion-null mice: Association with reduced afterhyperpolarizations in CA1 hippocampal neurons

AU - Powell, Andrew

AU - Toescu, Emil

AU - Collinge, J

AU - Jefferys, John

PY - 2008/1/1

Y1 - 2008/1/1

N2 - 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.

AB - 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.

KW - prion

KW - transgenic

KW - endoplasmic reticulum

KW - hippocampus

KW - calcium signaling

KW - AHP

U2 - 10.1523/JNEUROSCI.0675-08.2008

DO - 10.1523/JNEUROSCI.0675-08.2008

M3 - Article

C2 - 18400886

VL - 28

SP - 3877

EP - 3886

JO - The Journal of Neuroscience

JF - The Journal of Neuroscience

SN - 0270-6474

IS - 15

ER -