Inhibition by Propofol of Intracellular Calcium Mobilization in Cultured Mouse Pituitary Cells

Deau, Jacques T. Ya; Morelli, Christine M.; Desravines, Soléenne

doi:10.1213/01.ane.0000082240.74557.6d

Cited by 10 publications

(6 citation statements)

References 23 publications

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“…1 and 2). This conclusion is consistent with other observations showing that low concentrations of propofol have little effect on the processes governing transmitter release from axon terminals (Mantz et al 1995;Olcese et al 1994;Shirasaka et al 2004;Takei et al 2003;Westphalen and Hemmings 2003;Ya Deau et al 2003;reviewed by Richards 2002).…”

Section: Enhancement Of Gabaergic Input Is Primarily Mediated Throughsupporting

confidence: 92%

Propofol-Block of SK Channels in Reticular Thalamic Neurons Enhances GABAergic Inhibition in Relay Neurons

Ying

Goldstein²

2005

Journal of Neurophysiology

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The GABAergic reticular thalamic nucleus (RTN) is a major source of inhibition for thalamocortical neurons in the ventrobasal complex (VB). Thalamic circuits are thought to be an important anatomic target for general anesthetics. We investigated presynaptic actions of the intravenous anesthetic propofol in RTN neurons, using RTN-retained and RTN-removed brain slices. In RTN-retained slices, focal and bath application of propofol increased intrinsic excitability, temporal summation, and spike firing rate in RTN neurons. Propofol-induced activation was associated with suppression of medium afterhyperpolarization potentials. This activation was mimicked and completely occluded by the small conductance calcium-activated potassium (SK) channel blocker apamin, indicating that propofol could enhance RTN excitability by blocking SK channels. Propofol increased GABAergic transmission at RTN-VB synapses, consistent with excitation of presynaptic RTN neurons. Stimulation of RTN resulted in synaptic inhibition in postsynaptic neurons in VB, and this inhibition was potentiated by propofol in a concentration-dependent manner. Removal of RTN resulted in a dramatic reduction of both spontaneous postsynaptic inhibitory current frequency and propofol-mediated inhibition of VB neurons. Thus the existence and activation of RTN input were essential for propofol to elicit thalamocortical suppression; such suppression resulted from shunting through the postsynaptic GABA(A) receptor-mediated chloride conductance. The results indicate that propofol enhancement of RTN-mediated inhibitory input via blockade of SK channels may play a critical role in "gating" spike firing in thalamocortical relay neurons.

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Section: Enhancement Of Gabaergic Input Is Primarily Mediated Throughsupporting

confidence: 92%

Propofol-Block of SK Channels in Reticular Thalamic Neurons Enhances GABAergic Inhibition in Relay Neurons

Ying

Goldstein²

2005

Journal of Neurophysiology

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“…Systemic hypotension caused by a marked decrease in systemic vascular resistance is often observed in the clinical use of propofol, probably via a decrease in [Ca 2+ ] i . The negative inotropic and vasodilatory effects associated with propofol are likely due the voltage-gated influx of extracellular calcium being blocked, and to the decrease in availability of intracellular calcium (1, 4). Propofol affects [Ca 2+ ] i by inhibiting the mobilization of intracellular-calcium stores (6).…”

Section: Discussionmentioning

confidence: 99%

Propofol and Aminophylline Antagonize Each Other During the Mobilization of Intracellular Calcium in Human Umbilical Vein Endothelial Cells

Son

Lim

et al. 2010

J Korean Med Sci

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This study examined whether propofol and aminophylline affect the mobilization of intracellular calcium in human umbilical vein endothelial cells. Intracellular calcium was measured using laser scanning confocal microscopy. Cultured and serum-starved cells on round coverslips were incubated with propofol or aminophylline for 30 min, and then stimulated with lysophosphatidic acid, propofol and aminophylline. The results were expressed as relative fluorescence intensity and fold stimulation. Propofol decreased the concentration of intracellular calcium, whereas aminophylline caused increased mobilization of intracellular calcium in a concentration-dependent manner. Propofol suppressed the lysophosphatidic acid-induced mobilization of intracellular calcium in a concentration-dependent manner. Propofol further prevented the aminophylline-induced increase of intracellular calcium at clinically relevant concentrations. However, aminophylline reversed the inhibitory effect of propofol on the elevation of intracellular calcium by lysophosphatidic acid. Our results suggest that propofol and aminophylline antagonize each other on the mobilization of intracellular calcium in human umbilical vein endothelial cells at clinically relevant concentrations. Serious consideration should be given to how this interaction affects mobilization of intracellular calcium when these two drugs are used together.

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“…2B), independently confirming that BI-1 overexpression regulates ER Ca we cultured HT1080 cells in Ca 2ϩ -free medium and then treated them with a 5 g/ml concentration of the detergent digitonin (digitonin at 5 g/ml did not cause any leakage of Fura-2 florescence; data not shown) and the Ca 2ϩ ionophore ionomycin. Digitonin can permeabilize the cell membranes to small molecules such as Ca 2ϩ (14,15) and allows indirect measurement of intra-ER calcium with ionomycin. In BI-1-expressing cells, maximal [Ca 2ϩ ] i induced by ionomycin was approximately half the levels of control cells (p Ͻ 0.05 by unpaired t test).…”

Section: Measurement Of Intracellular Ca 2ϩmentioning

confidence: 99%

Bax Inhibitor-1 Is a pH-dependent Regulator of Ca2+ Channel Activity in the Endoplasmic Reticulum

Kim

Lee

et al. 2008

Journal of Biological Chemistry

104

134

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In this study, Bax inhibitor-1 (BI-1release from ER microsomes from BI-1-overexpressing cells and BI-1-reconsituted liposomes. Acidic conditions also induced BI-1 protein oligomerization. Interestingly subjecting BI-1-overexpressing cells to acidic conditions induced more Bax recruitment to mitochondria, more cytochrome c release from mitochondria, and more cell death. These findings suggest that BI-1 increases Ca 2؉ leak rates from the ER through a mechanism that is dependent on pH and on the carboxyl-terminal cytosolic region of the BI-1 protein. The findings also reveal a cell death-promoting phenotype for BI-1 that is manifested under low pH conditions. The endoplasmic reticulum (ER)3 contains the largest calcium reserve in the cell (1, 2). Agonist-induced ER calcium release occurs through Ca 2ϩ channels such as inositol trisphosphate (IP 3 ) and ryanodine receptors (3). Calcium uptake into the ER occurs when the calcium release channels are closed (i.e. negative feedback to the IP 3 receptor) (4) and is performed by sarcoplasmic reticulum/ER-associated calcium-activated ATPase pumps (5). In the resting state, the Ca 2ϩ content of the ER reflects a balance between active uptake by sarcoplasmic reticulum/ER-associated calcium-activated ATPase and passive efflux or basal leakage through other Ca 2ϩ channels. This leakage is revealed when sarcoplasmic reticulum/ER-associated calcium-activated ATPase pumps are inhibited by agents such as thapsigargin (6), causing Ca 2ϩ to leak out of the ER into the cytosol.The Bax inhibitor-1 (BI-1) (also known as "testis enhanced gene transcript" (TEGT)) is an antiapoptotic protein capable of inhibiting Bax activation and translocation to mitochondria (7). This ubiquitously expressed protein contains several transmembrane domains and localizes to the ER. The homology of BI-1 sequences among species is striking, and the characteristic hydrophobicity and ER membrane localization are evolutionarily conserved (8). BI-1 affects calcium leakage from the ER as measured with Ca 2ϩ -sensitive, ER-targeted fluorescent proteins and Ca 2ϩ -sensitive dyes (9). However, the mechanism by which BI-1 regulates ER Ca 2ϩ fluxes remains unclear. Here we have provided additional evidence that BI-1 induces passive Ca 2ϩ leakage from the ER and also show that BI-1 activity is regulated by pH in a manner dependent on the carboxyl-terminal cytosolic domain of this protein.* This work was supported, in whole or in part, by National Institutes of Health Grant AG15393 (to J. C. R.). This work was also supported by Korea Research Foundation Grants KRF-2005-070-C00095, E00021, and 2005-015-E00210 and Korea Science and Engineering Foundation Grants R01-2006-000-10422-0 and R01-2007-000-20275-0. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Inhibition by Propofol of Intracellular Calcium Mobilization in Cultured Mouse Pituitary Cells

Cited by 10 publications

References 23 publications

Propofol-Block of SK Channels in Reticular Thalamic Neurons Enhances GABAergic Inhibition in Relay Neurons

Propofol-Block of SK Channels in Reticular Thalamic Neurons Enhances GABAergic Inhibition in Relay Neurons

Propofol and Aminophylline Antagonize Each Other During the Mobilization of Intracellular Calcium in Human Umbilical Vein Endothelial Cells

Bax Inhibitor-1 Is a pH-dependent Regulator of Ca2+ Channel Activity in the Endoplasmic Reticulum

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