Activation of Protein Kinase C in Sensory Neurons Accelerates Ca<sup>2+</sup>Uptake into the Endoplasmic Reticulum

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

doi:10.1523/jneurosci.2920-05.2006

Cited by 41 publications

(36 citation statements)

References 71 publications

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“…Although SERCA activity has been reported to be increased by PKC activation in others cells [46], we believe our results provide the first evidence for the regulation of SERCA by PKC in intact platelets under the control of physiological agonists. It is possible that this regulation may be direct as phosphoproteomic profiling of platelets has previously shown a serine phosphorylation of SERCA2 [47].…”

Section: Discussionmentioning

confidence: 44%

Conventional protein kinase C isoforms differentially regulate ADP- and thrombin-evoked Ca2+ signalling in human platelets

et al. 2015

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Rises in cytosolic Ca 2+ concentration ([Ca 2+ ] cyt ) are central in platelet activation, yet many aspects of the underlying mechanisms are poorly understood. Most studies examine how experimental manipulations affect agonist-evoked rises in [Ca 2+ ] cyt , but these only monitor the net effect of manipulations on the processes controlling [Ca 2+ ] cyt (Ca 2+ buffering, sequestration, release, entry and removal), and cannot resolve the source of the Ca 2+ or the transporters or channels affected. To investigate the effects of protein kinase C (PKC) on platelet Ca 2+ signalling, we here monitor Ca 2+ flux around the platelet by measuring net Ca 2+ fluxes to or from the extracellular space and the intracellular Ca 2+ stores, which act as the major sources and sinks for Ca 2+ influx into and efflux from the cytosol, as well as monitoring the cytosolic Na + concentration ([Na + ] cyt ), which influences platelet Ca 2+ fluxes via Na + /Ca 2+ exchange. The intracellular store Ca 2+ concentration ([Ca 2+ ] st ) was monitored using Fluo-5N, the extracellular Ca 2+ concentration ([Ca 2+ ] ext ) was monitored using Fluo-4 whilst [Ca 2+ ] cyt and [Na + ] cyt were monitored using Fura-2 and SFBI respectively. PKC inhibition using Ro-31-8220 or bisindolaemide I potentiated ADP-and thrombin-evoked rises in [Ca 2+ ] cyt in the absence of extracellular Ca 2+ . PKC inhibition potentiated ADP-evoked but reduced thrombin-evoked intracellular Ca 2+ release and Ca 2+ removal into the extracellular medium. SERCA inhibition using thapsigargin and 2,5-di(tert-butyl) l,4-benzohydroquinone abolished the effect of PKC inhibitors on ADP-evoked changes in [Ca 2+ ] cyt but only reduced the effect on thrombin-evoked responses. Thrombin evokes substantial rises in [Na + ] cyt which would be expected to reduce Ca 2+ removal via the Na + /Ca 2+ exchanger (NCX). Thrombinevoked rises in [Na + ] cyt were potentiated by PKC inhibition, an effect which was not due to altered changes in non-selective cation permeability of the plasma membrane as assessed by Mn 2+ quench of Fura-2 fluorescence. PKC inhibition was without effect on thrombin-evoked rises in [Ca 2+ ] cyt following SERCA inhibition and either removal of extracellular Na + or inhibition of Na + /K + -ATPase activity by removal of extracellular K + or treatment with digoxin. These data suggest that PKC limits ADP-evoked rises in [Ca 2+ ] cyt by acceleration of SERCA activity, whilst rises in [Ca 2+ ] cyt evoked by the stronger platelet activator thrombin are limited by PKC through acceleration of both SERCA and Na + /K + -ATPase activity, with the latter limiting the effect of thrombin on rises in [Na + ] cyt and so forward mode NCX activity. The use of selective PKC inhibitors indicated that conventional and not novel PKC isoforms are responsible for the inhibition of agonist-evoked Ca 2+ signalling.

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Section: Discussionmentioning

confidence: 44%

Conventional protein kinase C isoforms differentially regulate ADP- and thrombin-evoked Ca2+ signalling in human platelets

et al. 2015

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“…Ca 2ϩ buffering mechanisms in neurons include: extrusion across plasma membrane, binding to mobile and immobile cytoplasmic buffers and uptake into intracellular stores such as mitochondria and endoplasmic reticulum (Neher, 1998). The ER functions as a major Ca 2ϩ uptake mechanism in neurons (Neering and McBurney, 1984;Sabatini et al, 2002;Usachev et al, 2006). This functional role for the ER coupled with the observations that PrP is widely expressed in the ER (Holscher et al, 2001), and that the ER has been implicated in the aberrant response of Prnp 0/0 neurons to oxidative stress (Krebs et al, 2007), led us to hypothesize that changes in the function of the ER may underlie the observed alterations in Ca 2ϩ homeostasis.…”

Section: Camentioning

confidence: 99%

Alterations in Ca²⁺-Buffering in Prion-Null Mice: Association with Reduced Afterhyperpolarizations in CA1 Hippocampal Neurons

Powell¹,

Toescu²,

Collinge³

et al. 2008

J. Neurosci.

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“…We suggest that the duration of Ca 2ϩ elevation was too brief for PMA to significantly enhance ASTIC generation. Phorbol ester treatment also is suggested to enhance neuronal clearance of cytosolic Ca 2ϩ (28). This latter action could potentially shorten the duration of the caffeineevoked Ca 2ϩ transient and counteract any potentiating effect on ASTIC generation.…”

Section: Discussionmentioning

confidence: 99%

Somatic ATP release from guinea pig sympathetic neurons does not require calcium-induced calcium release from internal stores

Merriam

Locknar

Girard

et al. 2010

American Journal of Physiology-Cell Physiology

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Activation of Protein Kinase C in Sensory Neurons Accelerates Ca²⁺Uptake into the Endoplasmic Reticulum

Abstract: PKC inhibitors GF109203x (2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)maleimide) and calphostin. PKC-dependent acceleration

Cited by 41 publications

References 71 publications

Conventional protein kinase C isoforms differentially regulate ADP- and thrombin-evoked Ca2+ signalling in human platelets

Conventional protein kinase C isoforms differentially regulate ADP- and thrombin-evoked Ca2+ signalling in human platelets

Alterations in Ca²⁺-Buffering in Prion-Null Mice: Association with Reduced Afterhyperpolarizations in CA1 Hippocampal Neurons

Somatic ATP release from guinea pig sympathetic neurons does not require calcium-induced calcium release from internal stores

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Activation of Protein Kinase C in Sensory Neurons Accelerates Ca2+Uptake into the Endoplasmic Reticulum

Abstract: PKC inhibitors GF109203x (2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)maleimide) and calphostin. PKC-dependent acceleration

Cited by 41 publications

References 71 publications

Conventional protein kinase C isoforms differentially regulate ADP- and thrombin-evoked Ca2+ signalling in human platelets

Conventional protein kinase C isoforms differentially regulate ADP- and thrombin-evoked Ca2+ signalling in human platelets

Alterations in Ca2+-Buffering in Prion-Null Mice: Association with Reduced Afterhyperpolarizations in CA1 Hippocampal Neurons

Somatic ATP release from guinea pig sympathetic neurons does not require calcium-induced calcium release from internal stores

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Activation of Protein Kinase C in Sensory Neurons Accelerates Ca²⁺Uptake into the Endoplasmic Reticulum

Alterations in Ca²⁺-Buffering in Prion-Null Mice: Association with Reduced Afterhyperpolarizations in CA1 Hippocampal Neurons