Methacholine and PDGF activate store-operated calcium entry in neuronal precursor cells via distinct calcium entry channels

Neurons are a diverse cell type exhibiting hugely different morphologies and neurotransmitter specifications. Their distinctive phenotypes are established during differentiation from pluripotent precursor cells. The signalling pathways that specify the lineage down which neuronal precursor cells dif...

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Main Authors: PAUL CUDDON, MARTIN D BOOTMAN, GILLIAN R RICHARDS, ALISON J SMITH, PETER B SIMPSON, H LLEWELYN RODERICK
Format: Article
Language:English
Published: BMC 2008-01-01
Series:Biological Research
Subjects:
Online Access:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602008000200008
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author PAUL CUDDON
MARTIN D BOOTMAN
GILLIAN R RICHARDS
ALISON J SMITH
PETER B SIMPSON
H LLEWELYN RODERICK
author_facet PAUL CUDDON
MARTIN D BOOTMAN
GILLIAN R RICHARDS
ALISON J SMITH
PETER B SIMPSON
H LLEWELYN RODERICK
author_sort PAUL CUDDON
collection DOAJ
description Neurons are a diverse cell type exhibiting hugely different morphologies and neurotransmitter specifications. Their distinctive phenotypes are established during differentiation from pluripotent precursor cells. The signalling pathways that specify the lineage down which neuronal precursor cells differentiate remain to be fully elucidated. Among the many signáis that impinge on the differentiation of neuronal cells, cytosolic calcium (Ca2+) has an important role. However, little is known about the nature of the Ca2+ signáis involved in fate choice in neuronal precursor cells, or their sources. In this study, we show that activation of either muscarinic or platelet-derived growth factor (PDGF) receptors induces a biphasic increase in cytosolic Ca2+ that consists of reléase from intracellular stores followed by sustained entry across the plasma membrane. For both agonists, the prolonged Ca2+ entry occurred via a store-operated pathway that was pharmacologically indistinguishable from Ca2+ entry initiated by thapsigargin. However, muscarinic receptor-activated Ca2+ entry was inhibited by siRNA-mediated knockdown of TRPC6, whereas Ca2+ entry evoked by PDGF was not. These data provide evidence for agonist-specific activation of molecularly distinct store-operated Ca2+ entry pathways, and raise the possibility of privileged communication between these Ca2+ entry pathways and downstream processes.
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spelling doaj.art-5b2950a7db644d21b4067656dd054e832022-12-21T23:41:36ZengBMCBiological Research0716-97600717-62872008-01-01412183195Methacholine and PDGF activate store-operated calcium entry in neuronal precursor cells via distinct calcium entry channelsPAUL CUDDONMARTIN D BOOTMANGILLIAN R RICHARDSALISON J SMITHPETER B SIMPSONH LLEWELYN RODERICKNeurons are a diverse cell type exhibiting hugely different morphologies and neurotransmitter specifications. Their distinctive phenotypes are established during differentiation from pluripotent precursor cells. The signalling pathways that specify the lineage down which neuronal precursor cells differentiate remain to be fully elucidated. Among the many signáis that impinge on the differentiation of neuronal cells, cytosolic calcium (Ca2+) has an important role. However, little is known about the nature of the Ca2+ signáis involved in fate choice in neuronal precursor cells, or their sources. In this study, we show that activation of either muscarinic or platelet-derived growth factor (PDGF) receptors induces a biphasic increase in cytosolic Ca2+ that consists of reléase from intracellular stores followed by sustained entry across the plasma membrane. For both agonists, the prolonged Ca2+ entry occurred via a store-operated pathway that was pharmacologically indistinguishable from Ca2+ entry initiated by thapsigargin. However, muscarinic receptor-activated Ca2+ entry was inhibited by siRNA-mediated knockdown of TRPC6, whereas Ca2+ entry evoked by PDGF was not. These data provide evidence for agonist-specific activation of molecularly distinct store-operated Ca2+ entry pathways, and raise the possibility of privileged communication between these Ca2+ entry pathways and downstream processes.http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602008000200008Ca2+PDGFmethacholineTRPC6SOCEhuman neurosphere-derived cells
spellingShingle PAUL CUDDON
MARTIN D BOOTMAN
GILLIAN R RICHARDS
ALISON J SMITH
PETER B SIMPSON
H LLEWELYN RODERICK
Methacholine and PDGF activate store-operated calcium entry in neuronal precursor cells via distinct calcium entry channels
Biological Research
Ca2+
PDGF
methacholine
TRPC6
SOCE
human neurosphere-derived cells
title Methacholine and PDGF activate store-operated calcium entry in neuronal precursor cells via distinct calcium entry channels
title_full Methacholine and PDGF activate store-operated calcium entry in neuronal precursor cells via distinct calcium entry channels
title_fullStr Methacholine and PDGF activate store-operated calcium entry in neuronal precursor cells via distinct calcium entry channels
title_full_unstemmed Methacholine and PDGF activate store-operated calcium entry in neuronal precursor cells via distinct calcium entry channels
title_short Methacholine and PDGF activate store-operated calcium entry in neuronal precursor cells via distinct calcium entry channels
title_sort methacholine and pdgf activate store operated calcium entry in neuronal precursor cells via distinct calcium entry channels
topic Ca2+
PDGF
methacholine
TRPC6
SOCE
human neurosphere-derived cells
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602008000200008
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