Point mutation in the mouse P2X7 receptor affects intercellular calcium waves in astrocytes.

Sylvia O. Suadicani, Rodolfo Iglesias, David C. Spray, Eliana Scemes

Research output: Contribution to journalArticle

Abstract

Purinergic P2 receptors and gap junctions are two groups of proteins involved in the transmission of ICWs (intercellular calcium waves) between astrocytes. The extent to which ICWs spread among these glial cells depends on the amount of ATP released, which can occur through membrane channels, as well as other pathways. Our previous studies have shown that the pore-forming P2X7R (P2X7 receptor) contributes to the amplification of ICW spread by providing sites of ATP release through Panx1 (Pannexin1) channels. To gain insight into the signal transduction events mediating this response we compared the properties of the P2X7R-Panx1 complex in astrocytes from a mouse strain (C57Bl/6) containing a naturally occurring point mutation (P451L) in the C-terminus of the P2X7R to that of non-mutated receptors (Balb/C mice). Electrophysiological, biochemical, pharmacological and fluorescence imaging techniques revealed that the P451L mutation located in the SH3 domain (a Src tyrosine kinase-binding site) of the C-terminus of the P2X7R attenuates Panx1 currents, ATP release and the distance of ICW spread between astrocytes. Similar results were obtained when using the Src tyrosine inhibitor (PP2) and a membrane-permeant peptide spanning the P451L mutation of the P2X7R of the C57Bl6 astrocytes. These results support the participation of a tyrosine kinase of the Src family in the initial steps mediating the opening of Panx1 channels following P2X7R stimulation and in the transmission of calcium signals among astrocytes.

Original languageEnglish (US)
JournalASN Neuro
Volume1
Issue number1
StatePublished - 2009
Externally publishedYes

Fingerprint

Purinergic P2X7 Receptors
Calcium Signaling
Point Mutation
Astrocytes
src-Family Kinases
Adenosine Triphosphate
Purinergic P2 Receptors
Mutation
src Homology Domains
Gap Junctions
Optical Imaging
Ion Channels
Neuroglia
Tyrosine
Signal Transduction
Binding Sites
Pharmacology
Calcium
Peptides
Membranes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Point mutation in the mouse P2X7 receptor affects intercellular calcium waves in astrocytes. / Suadicani, Sylvia O.; Iglesias, Rodolfo; Spray, David C.; Scemes, Eliana.

In: ASN Neuro, Vol. 1, No. 1, 2009.

Research output: Contribution to journalArticle

@article{928d9253272841efba1abaf328d2a737,
title = "Point mutation in the mouse P2X7 receptor affects intercellular calcium waves in astrocytes.",
abstract = "Purinergic P2 receptors and gap junctions are two groups of proteins involved in the transmission of ICWs (intercellular calcium waves) between astrocytes. The extent to which ICWs spread among these glial cells depends on the amount of ATP released, which can occur through membrane channels, as well as other pathways. Our previous studies have shown that the pore-forming P2X7R (P2X7 receptor) contributes to the amplification of ICW spread by providing sites of ATP release through Panx1 (Pannexin1) channels. To gain insight into the signal transduction events mediating this response we compared the properties of the P2X7R-Panx1 complex in astrocytes from a mouse strain (C57Bl/6) containing a naturally occurring point mutation (P451L) in the C-terminus of the P2X7R to that of non-mutated receptors (Balb/C mice). Electrophysiological, biochemical, pharmacological and fluorescence imaging techniques revealed that the P451L mutation located in the SH3 domain (a Src tyrosine kinase-binding site) of the C-terminus of the P2X7R attenuates Panx1 currents, ATP release and the distance of ICW spread between astrocytes. Similar results were obtained when using the Src tyrosine inhibitor (PP2) and a membrane-permeant peptide spanning the P451L mutation of the P2X7R of the C57Bl6 astrocytes. These results support the participation of a tyrosine kinase of the Src family in the initial steps mediating the opening of Panx1 channels following P2X7R stimulation and in the transmission of calcium signals among astrocytes.",
author = "Suadicani, {Sylvia O.} and Rodolfo Iglesias and Spray, {David C.} and Eliana Scemes",
year = "2009",
language = "English (US)",
volume = "1",
journal = "ASN Neuro",
issn = "1759-0914",
publisher = "Portland Press Ltd.",
number = "1",

}

TY - JOUR

T1 - Point mutation in the mouse P2X7 receptor affects intercellular calcium waves in astrocytes.

AU - Suadicani, Sylvia O.

AU - Iglesias, Rodolfo

AU - Spray, David C.

AU - Scemes, Eliana

PY - 2009

Y1 - 2009

N2 - Purinergic P2 receptors and gap junctions are two groups of proteins involved in the transmission of ICWs (intercellular calcium waves) between astrocytes. The extent to which ICWs spread among these glial cells depends on the amount of ATP released, which can occur through membrane channels, as well as other pathways. Our previous studies have shown that the pore-forming P2X7R (P2X7 receptor) contributes to the amplification of ICW spread by providing sites of ATP release through Panx1 (Pannexin1) channels. To gain insight into the signal transduction events mediating this response we compared the properties of the P2X7R-Panx1 complex in astrocytes from a mouse strain (C57Bl/6) containing a naturally occurring point mutation (P451L) in the C-terminus of the P2X7R to that of non-mutated receptors (Balb/C mice). Electrophysiological, biochemical, pharmacological and fluorescence imaging techniques revealed that the P451L mutation located in the SH3 domain (a Src tyrosine kinase-binding site) of the C-terminus of the P2X7R attenuates Panx1 currents, ATP release and the distance of ICW spread between astrocytes. Similar results were obtained when using the Src tyrosine inhibitor (PP2) and a membrane-permeant peptide spanning the P451L mutation of the P2X7R of the C57Bl6 astrocytes. These results support the participation of a tyrosine kinase of the Src family in the initial steps mediating the opening of Panx1 channels following P2X7R stimulation and in the transmission of calcium signals among astrocytes.

AB - Purinergic P2 receptors and gap junctions are two groups of proteins involved in the transmission of ICWs (intercellular calcium waves) between astrocytes. The extent to which ICWs spread among these glial cells depends on the amount of ATP released, which can occur through membrane channels, as well as other pathways. Our previous studies have shown that the pore-forming P2X7R (P2X7 receptor) contributes to the amplification of ICW spread by providing sites of ATP release through Panx1 (Pannexin1) channels. To gain insight into the signal transduction events mediating this response we compared the properties of the P2X7R-Panx1 complex in astrocytes from a mouse strain (C57Bl/6) containing a naturally occurring point mutation (P451L) in the C-terminus of the P2X7R to that of non-mutated receptors (Balb/C mice). Electrophysiological, biochemical, pharmacological and fluorescence imaging techniques revealed that the P451L mutation located in the SH3 domain (a Src tyrosine kinase-binding site) of the C-terminus of the P2X7R attenuates Panx1 currents, ATP release and the distance of ICW spread between astrocytes. Similar results were obtained when using the Src tyrosine inhibitor (PP2) and a membrane-permeant peptide spanning the P451L mutation of the P2X7R of the C57Bl6 astrocytes. These results support the participation of a tyrosine kinase of the Src family in the initial steps mediating the opening of Panx1 channels following P2X7R stimulation and in the transmission of calcium signals among astrocytes.

UR - http://www.scopus.com/inward/record.url?scp=84855741434&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855741434&partnerID=8YFLogxK

M3 - Article

VL - 1

JO - ASN Neuro

JF - ASN Neuro

SN - 1759-0914

IS - 1

ER -