Activation of protein kinase C in sensory neurons accelerates Ca2+ uptake into the endoplasmic reticulum

Yuriy M Usachev; Anthony J Marsh; Tanner M Johanns; Michelle M Lemke; Stanley A Thayer

doi:10.1523/JNEUROSCI.2920-05.2006

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Activation of protein kinase C in sensory neurons accelerates Ca2+ uptake into the endoplasmic reticulum

Journal article

Open access

Peer reviewed

Activation of protein kinase C in sensory neurons accelerates Ca2+ uptake into the endoplasmic reticulum

Yuriy M Usachev, Anthony J Marsh, Tanner M Johanns, Michelle M Lemke and Stanley A Thayer

The Journal of neuroscience, Vol.26(1), pp.311-318

01/04/2006

DOI: 10.1523/JNEUROSCI.2920-05.2006

PMCID: PMC6674318

PMID: 16399701

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Abstract

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.

Endoplasmic Reticulum - enzymology

Calcium - metabolism

Cells, Cultured

Endoplasmic Reticulum - metabolism

Rats

Rats, Sprague-Dawley

Neurons, Afferent - enzymology

Action Potentials - physiology

Animals

Time Factors

Protein Kinase C - metabolism

Neurons, Afferent - metabolism

Enzyme Activation - physiology

Details

Title: Subtitle: Activation of protein kinase C in sensory neurons accelerates Ca2+ uptake into the endoplasmic reticulum
Creators: Yuriy M Usachev - Department of Pharmacology, University of Iowa, Iowa City, Iowa 52242, USA
Anthony J Marsh
Tanner M Johanns
Michelle M Lemke
Stanley A Thayer
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.26(1), pp.311-318
Publisher: United States
DOI: 10.1523/JNEUROSCI.2920-05.2006
PMID: 16399701
PMCID: PMC6674318
ISSN: 0270-6474
eISSN: 1529-2401
Grant note: R37 DA007304 / NIDA NIH HHS P50 DA011806 / NIDA NIH HHS DA07304 / NIDA NIH HHS R01 DA007304 / NIDA NIH HHS DA11806 / NIDA NIH HHS T32 DA007304 / NIDA NIH HHS
Language: English
Date published: 01/04/2006
Academic Unit: Iowa Neuroscience Institute; Anesthesia; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984070607302771

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