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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-1-9
pubmed:abstractText
The rate of Ca2+ clearance from the neuronal cytoplasm affects the amplitude, duration, and localization of Ca2+ signals and influences a variety of Ca2+-dependent functions. We reported previously that activation of protein kinase C (PKC) accelerates Ca2+ efflux in rat sensory neurons mediated by the plasma membrane Ca2+-ATPase isoform 4 (PMCA4). Here we show that sarco-endoplasmic reticulum Ca2+-ATPase (SERCA)-mediated Ca2+ uptake into intracellular stores is also accelerated by PKC activation. The rate of intracellular Ca2+ concentration ([Ca2+]i) clearance was studied after small (<350 nM) action potential-induced Ca2+ loads in rat dorsal root ganglion neurons. Under these conditions, mitochondrial Ca2+ uptake and Na+/Ca2+ exchange do not significantly influence [Ca2+]i recovery. Phorbol dibutyrate (PDBu) increased the rate of [Ca2+]i clearance by 71% in a manner sensitive to the selective PKC inhibitors GF109203x (2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)maleimide) and calphostin. PKC-dependent acceleration was still observed (approximately 39%) when the PKC-sensitive PMCA isoform was knocked down by expression of an antisense PMCA4 cDNA (AS4). Direct measurement of Ca2+ in the endoplasmic reticulum (ER) lumen revealed that PKC increased the rate of store refilling more than twofold after depletion by treatment with cyclopiazonic acid. ER refilling was less complete in PDBu-treated cells, although, in AS4-expressing cells, PDBu accelerated the rate without reducing the ER capacity, suggesting that PMCA and SERCA compete for Ca2+. Thus, activation of PKC accelerates the clearance of Ca2+ from the cytoplasm by the concerted stimulation of Ca2+ sequestration and Ca2+ efflux.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
4
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
311-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Activation of protein kinase C in sensory neurons accelerates Ca2+ uptake into the endoplasmic reticulum.
pubmed:affiliation
Department of Pharmacology, University of Iowa, Iowa City, Iowa 52242, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural