Intracellular Ca2+- and PKC-dependent upregulation of T-type Ca2+ channels in LPC-stimulated cardiomyocytes

Zheng, Mingqi; Wang, Yan; Kang, Lin; Shimaoka, Toru; Marni, Farzana; Ono, Katsushige

doi:10.1016/j.yjmcc.2009.08.032

Cited by 20 publications

(16 citation statements)

References 34 publications

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“…In contrast, Cav-3 overexpression inhibited the basal peak I Ca, T and abolished the Ang-II stimulation of peak I Ca, T (Ϫ2 Ϯ 0.7 pA/pF). Previous studies have demonstrated that PKC␣ activates and regulates the Ca v 3.2 channel current (33,34). Increased PKC␣ expression and signaling were reported in cardiac hypertrophy and heart failure (35,36).…”

Section: Cav-3 Knockdown Results In Increased Ang-ii Stimulation Of Imentioning

confidence: 97%

Caveolin-3 Overexpression Attenuates Cardiac Hypertrophy via Inhibition of T-type Ca2+ Current Modulated by Protein Kinase Cα in Cardiomyocytes

Markandeya

Phelan

Woon

et al. 2015

Journal of Biological Chemistry

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Section: Cav-3 Knockdown Results In Increased Ang-ii Stimulation Of Imentioning

confidence: 97%

Caveolin-3 Overexpression Attenuates Cardiac Hypertrophy via Inhibition of T-type Ca2+ Current Modulated by Protein Kinase Cα in Cardiomyocytes

Markandeya

Phelan

Woon

et al. 2015

Journal of Biological Chemistry

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“…In particular this might be due to concomitant PKC effects on transient sodium currents ( I Nat ) [40], which in turn directly influence voltage thresholds. Conflicting results have also been reported regarding the influence of PKC activation on I TCa [41,42]. However, changes in firing behavior do not rely on a modulation of I TCa in silico in pyramidal layer 5 neurons.…”

Section: Discussionmentioning

confidence: 99%

Protein kinase C activation mediates interferon-β-induced neuronal excitability changes in neocortical pyramidal neurons

Reetz

Stadler

Strauß

2014

J Neuroinflammation

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BackgroundCytokines are key players in the interactions of the immune and nervous systems. Recently, we showed that such interplay is mediated by type I interferons (IFNs), which elevate the excitability of neocortical pyramidal neurons. A line of indirect evidence suggested that modulation of multiple ion channels underlies the effect. However, which currents are principally involved and how the IFN signaling cascade is linked to the respective ion channels remains elusive.MethodsWe tested several single and combined ionic current modulations using an in silico model of a neocortical layer 5 neuron. Subsequently we investigated resulting predictions by whole-cell patch-clamp recordings in layer 5 neurons of ex vivo neocortical rat brain slices pharmacologically reproducing or prohibiting neuronal IFN effects.ResultsThe amount and type of modulation necessary to replicate IFN effects in silico suggested protein kinase C (PKC) activation as link between the type I IFN signaling and ion channel modulations. In line with this, PKC activation with 4β-phorbol 12-myristate 13-acetate (4β-PMA) or Bryostatin1 augmented the excitability of neocortical layer 5 neurons comparable to IFN-β in our ex vivo recordings. In detail, both PKC activators attenuated the rheobase and increased the input-output gain as well as the input resistance, thereby augmenting the neuronal excitability. Similar to IFN-β they also left the threshold of action potential generation unaffected. In further support of PKC mediating type I IFN effects, IFN-β, 4β-PMA and Bryostatin1 reduced the amplitude of post-train after-hyperpolarizations in a similar manner. In conjunction with this finding, IFN-β reduced M-currents, which contribute to after-hyperpolarizations and are modulated by PKC. Finally, blocking PKC activation with GF109203X at the catalytic site or calphostin C at the regulatory site prevented the main excitatory effects of IFN-β.ConclusionMultiple ion channel modulations underlie the neuromodulatory effect of type I IFNs. PKC activation is both sufficient and necessary for mediating the effect, and links the IFN signaling cascade to the intrinsic ion channels. Therefore, we regard PKC activation as unitary mechanism for the neuromodulatory potential of type I IFNs in neocortical neurons.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-014-0185-4) contains supplementary material, which is available to authorized users.

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“…In addition, it is known that lysoPC could cause the Ca 2+ -influx in rat cardiomyocytes [14]. LysoPC accumulation in intracellular and/or interstitial space in cardiomyocytes may underlie as a mechanism for tachycardia and various arrhythmias during cardiac ischemia, which is usually accompanied by elevation of [Ca 2+ ]i [2]. The exogenous lysoPC was also proven to induce myoischemia-like injury in in vitro study.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, lysoPC can induce the increase of the intracellular Ca 2+ concentration ([Ca 2+ ]i) and plays an important role in triggering onset of arrhythmias in cardiac ischemia [2]. Besides, lysoPC triggers apoptosis of vascular smooth muscle cells and endothelial cells by altering intracellular calcium signaling [3,4].…”

Section: Introductionmentioning

confidence: 99%

Baicalein, an active component of Scutellaria baicalensis Georgi, prevents lysophosphatidylcholine-induced cardiac injury by reducing reactive oxygen species production, calcium overload and apoptosis via MAPK pathways

Chen

Hsu

Liou

et al. 2014

BMC Complement Altern Med

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BackgroundLysophosphatidylcholine (lysoPC), a metabolite from membrane phospholipids, accumulates in the ischemic myocardium and plays an important role in the development of myocardial dysfunction ventricular arrhythmia. In this study, we investigated if baicalein, a major component of Huang Qui, can protect against lysoPC-induced cytotoxicity in rat H9c2 embryonic cardiomyocytes.MethodsCell viability was detected by the MTT assay; ROS levels were assessed using DCFH-DA; and intracellular free calcium concentrations were assayed by spectrofluorophotometer. Cell apoptosis and necrosis were evaluated by the flow cytometry assay and Hoechst staining. Mitogen-Activated Protein Kinases (MAPKs), which included the ERK, JNK, and p38, and the apoptotic mechanisms including Bcl-2/Bax, caspase-3, caspase-9 and cytochrome c pathways were examined by Western blot analysis. The activation of MAPKs was examined by enzyme-linked immunosorbent assay.ResultsWe found that lysoPC induced death and apoptosis of H9c2 cells in a dose-dependent manner. Baicalein could prevent lysoPC-induced cell death, production of reactive oxygen species (ROS), and increase of intracellular calcium concentration in H9c2 cardiomyoctes. In addition, baicalein also inhibited lysoPC-induced apoptosis, with associated decreased pro-apoptotic Bax protein, increased anti-apoptotic Bcl-2 protein, resulting in an increase in the Bcl-2/Bax ratio. Finally, baicalein attenuated lysoPC-induced the expression of cytochrome c, casapase-3, casapase-9, and the phosphorylations of ERK1/2, JNK, and p38. LysoPC-induced ERK1/2, JNK, and p38 activations were inhibited by baicalein.ConclusionsBaicalein protects cardiomyocytes from lysoPC-induced apoptosis by reducing ROS production, inhibition of calcium overload, and deactivations of MAPK signaling pathways.

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Intracellular Ca2+- and PKC-dependent upregulation of T-type Ca2+ channels in LPC-stimulated cardiomyocytes

Cited by 20 publications

References 34 publications

Caveolin-3 Overexpression Attenuates Cardiac Hypertrophy via Inhibition of T-type Ca2+ Current Modulated by Protein Kinase Cα in Cardiomyocytes

Caveolin-3 Overexpression Attenuates Cardiac Hypertrophy via Inhibition of T-type Ca2+ Current Modulated by Protein Kinase Cα in Cardiomyocytes

Protein kinase C activation mediates interferon-β-induced neuronal excitability changes in neocortical pyramidal neurons

Baicalein, an active component of Scutellaria baicalensis Georgi, prevents lysophosphatidylcholine-induced cardiac injury by reducing reactive oxygen species production, calcium overload and apoptosis via MAPK pathways

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