Publications (26)107.2 Total impact
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Article: Modulation of transient receptor potential melastatin related 7 channel by presenilins.
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ABSTRACT: Presenilins (PS1 and PS2) are multifunctional proteins involved in a diverse array of molecular and cellular functions, including proteolysis, development, neurogenesis, synaptic plasticity, ion channel regulation and phospholipid metabolism. Mutations in presenilin genes are responsible for the majority of Familial Alzheimer disease (FAD). Consequently, FAD-associated mutations in genes encoding PS1 or PS2 lead to several key cellular phenotypes, including alterations in proteolysis of β-amyloid precursor protein (APP) and Ca(2+) entry. The mechanism underlying presenilin (PS)-mediated modulation of Ca(2+) entry remains to be determined. Our previous studies showed that the PS-dependent down-regulation of phosphatidylinositol-4,5-bisphosphate (PIP2) is attributable to the observed Ca(2+) deficits. In this study, we attempted to identify the ion channel that is subject to the PIP2 and PS-dependent modulation. We found that Ca(2+) or Zn(2+) entry via the transient receptor potential melastatin 7 (TRPM7) channel was attenuated by the presence of FAD-associated PS1 mutants, such as ΔE9 and L286V. TRPM7 has been implicated in Mg(2+) homeostasis and embryonic development. The intracellular delivery of PIP2 restored TRPM7-mediated Ca(2+) influx, indicating that the observed deficits in Ca(2+) entry are due to downregulation of PIP2. Conversely, PS1 and PS2 deficiency, previously shown to upregulate PIP2 levels, potentiated TRPM7-mediated Ca(2+) influx. PS-dependent changes in Ca(2+) influx could be neutralized by a TRPM7 channel blocker. Collectively, these results indicate that TRPM7 may underlie the Ca(2+) entry deficits observed in FAD-associated PS mutants and suggest that the normal function of PS involves regulation of TRPM7 through a PIP2-dependent mechanism.Developmental Neurobiology 11/2011; 72(6):865-77. · 3.55 Impact Factor -
Article: Functional organization of dendritic Ca2+ signals in midbrain dopamine neurons.
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ABSTRACT: Dendritic Ca2+ plays an important role not only in synaptic integration and synaptic plasticity, but also in dendritic excitability in midbrain dopamine neurons. However, the functional organization of dendritic Ca2+ signals in the dopamine neurons remains largely unknown. We therefore investigated dendritic Ca2+ signals by measuring glutamate-induced Ca2+ increases along the dendrites of acutely isolated midbrain dopamine neurons. Maximal doses of glutamate induced a [Ca2+]c rise with similar amplitudes in proximal and distal dendritic regions of a dopamine neuron. Glutamate receptors contributed incrementally to the [Ca2+]c rise according to their distance from the soma, with a reciprocal decrement in the contribution of voltage-operated Ca2+ channels (VOCCs). The contribution of AMPA and NMDA receptors increased with dendritic length, but that of metabotropic glutamate receptors decreased. At low doses of glutamate at which spontaneous firing was sustained, the [Ca2+]c rise was higher in the distal than the proximal regions of a dendrite, possibly due to the increased spontaneous firing rate. These results indicate that functional organization of Ca2+ signals in the dendrites of dopamine neurons requires different combination of VOCCs and glutamate receptors according to dendritic length, and that regional Ca2+ rises in dendrites respond differently to applied glutamate concentration.Cell calcium 07/2011; 50(4):370-80. · 4.29 Impact Factor -
Article: Regulation of dopaminergic neuron firing by heterogeneous dopamine autoreceptors in the substantia nigra pars compacta.
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ABSTRACT: Dopamine (DA) receptors generate many cellular signals and play various roles in locomotion, motivation, hormone production, and drug abuse. According to the location and expression types of the receptors in the brain, DA signals act in either stimulatory or inhibitory manners. Although DA autoreceptors in the substantia nigra pars compacta are known to regulate firing activity, the exact expression patterns and roles of DA autoreceptor types on the firing activity are highly debated. Therefore, we performed individual correlation studies between firing activity and receptor expression patterns using acutely isolated rat substantia nigra pars compacta DA neurons. When we performed single-cell RT-PCR experiments, D(1), D(2)S, D(2)L, D(3), and D(5) receptor mRNA were heterogeneously expressed in the order of D(2)L > D(2)S > D(3) > D(5) > D(1). Stimulation of D(2) receptors with quinpirole suppressed spontaneous firing similarly among all neurons expressing mRNA solely for D(2)S, D(2)L, or D(3) receptors. However, quinpirole most strongly suppressed spontaneous firing in the neurons expressing mRNA for both D(2) and D(3) receptors. These data suggest that D(2) S, D(2)L, and D(3) receptors are able to equally suppress firing activity, but that D(2) and D(3) receptors synergistically suppress firing. This diversity in DA autoreceptors could explain the various actions of DA in the brain.Journal of Neurochemistry 11/2010; 116(6):966-74. · 4.06 Impact Factor -
Article: Protective effect of urocortin on 1-methyl-4-phenylpyridinium-induced dopaminergic neuronal death.
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ABSTRACT: Recent studies have indicated that the corticotropin releasing hormone (CRF)-related peptide, urocortin, restores key indicators of damage in animal models for Parkinson's disease (PD). However, the molecular mechanism for the neuroprotective effect of urocortin is unknown. 1-Methy-4-phenylpyridinium (MPP(+)) induces dopaminergic neuronal death. In the present study, MPP(+)-induced neuroblastoma SH-SY5Y cell death was significantly attenuated by urocortin in a concentration-dependent manner. The protective effect of urocortin involved the activation of CRF receptor type 1, resulting in the increase of cyclic AMP (cAMP) levels. Various cAMP-enhancing reagents mimicked the effect of urocortin, while inhibitors for protein kinase A (PKA) blocked the effect of urocortin, strongly implicating the involvement of cAMP-PKA pathway in the neuroprotective effect of urocortin on MPP(+)-induced cell death. As the downstream of this signal pathway, urocortin promoted phosphorylation of both glycogen synthase kinase 3β and extracellular signal-regulated kinases, which are known to promote cell survival. These neuroprotective signaling pathways of urocortin may serve as potential therapeutic targets for PD.Molecules and Cells 11/2010; 30(5):427-33. · 2.18 Impact Factor -
Article: Cholesterol inhibits M-type K+ channels via protein kinase C-dependent phosphorylation in sympathetic neurons.
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ABSTRACT: M-type (KCNQ) potassium channels play an important role in regulating the action potential firing in neurons. Here, we investigated the effect of cholesterol on M current in superior cervical ganglion (SCG) sympathetic neurons, using the patch clamp technique. M current was inhibited in a dose-dependent manner by cholesterol loading with a methyl-beta-cyclodextrin-cholesterol complex. This effect was prevented when membrane cholesterol level was restored by including empty methyl-beta-cyclodextrin in the pipette solution. Dialysis of cells with AMP-PNP instead of ATP prevented cholesterol action on M currents. Protein kinase C (PKC) inhibitor, calphostin C, abolished cholesterol-induced inhibition whereas the PKC activator, PDBu, mimicked the inhibition of M currents by cholesterol. The in vitro kinase assay showed that KCNQ2 subunits of M channel can be phosphorylated by PKC. A KCNQ2 mutant that is defective in phosphorylation by PKC failed to show current inhibition not only by PDBu but also by cholesterol. These results indicate that cholesterol-induced inhibition of M currents is mediated by PKC phosphorylation. The inhibition of M currents by PDBu and cholesterol was completely blocked by PIP(2) loading, indicating that the decrease in PIP(2)-channel interaction underlies M channel inhibition by PKC-mediated phosphorylation. We conclude that cholesterol specifically regulates M currents in SCG neurons via PKC activation.Journal of Biological Chemistry 04/2010; 285(14):10939-50. · 4.77 Impact Factor -
Article: Cholesterol modulates ion channels via down‐regulation of phosphatidylinositol 4,5‐bisphosphate
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ABSTRACT: J. Neurochem. (2010) 112, 1286–1294.AbstractUbiquitously expressed Mg2+-inhibitory cation (MIC) channels are permeable to Ca2+ and Mg2+ and are essential for cell viability. When membrane cholesterol level was increased by pre-incubating cells with a water-soluble form of cholesterol, the endogenous MIC current in HEK293 cells was negatively regulated. The application of phosphatidylinositol 4,5-bisphosphate (PIP2) recovered MIC current from cholesterol effect. As PIP2 is the direct modulator for MIC channels, high cholesterol content may cause down-regulation of PIP2. To test this possibility, we examined the effect of cholesterol on two exogenously expressed PIP2-sensitive K+ channels: human Ether-a-go-go related gene (HERG) and KCNQ. Enrichment with cholesterol inhibited HERG currents, while inclusion of PIP2 in the pipette solution blocked the cholesterol effect. KCNQ channel was also inhibited by cholesterol. The effects of cholesterol on these channels were blocked by pre-incubating cells with inhibitors for phospholipase C, which may indicate that cholesterol enrichment induces the depletion of PIP2 via phospholipase C activation. Lipid analysis showed that cholesterol enrichment reduced γ-32P incorporation into PIP2 by approximately 35%. Our results suggest that cholesterol may modulate ion channels by changing the levels of PIP2. Thus, an important cross-talk exists among two plasma membrane-enriched lipids, cholesterol and PIP2.Journal of Neurochemistry 12/2009; 112(5):1286 - 1294. · 4.06 Impact Factor -
Article: Cholesterol modulates ion channels via down-regulation of phosphatidylinositol 4,5-bisphosphate.
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ABSTRACT: Ubiquitously expressed Mg(2+)-inhibitory cation (MIC) channels are permeable to Ca2+ and Mg2+ and are essential for cell viability. When membrane cholesterol level was increased by pre-incubating cells with a water-soluble form of cholesterol, the endogenous MIC current in HEK293 cells was negatively regulated. The application of phosphatidylinositol 4,5-bisphosphate (PIP2) recovered MIC current from cholesterol effect. As PIP2 is the direct modulator for MIC channels, high cholesterol content may cause down-regulation of PIP2. To test this possibility, we examined the effect of cholesterol on two exogenously expressed PIP2-sensitive K+ channels: human Ether-a-go-go related gene (HERG) and KCNQ. Enrichment with cholesterol inhibited HERG currents, while inclusion of PIP2 in the pipette solution blocked the cholesterol effect. KCNQ channel was also inhibited by cholesterol. The effects of cholesterol on these channels were blocked by pre-incubating cells with inhibitors for phospholipase C, which may indicate that cholesterol enrichment induces the depletion of PIP2 via phospholipase C activation. Lipid analysis showed that cholesterol enrichment reduced gamma-(32)P incorporation into PIP2 by approximately 35%. Our results suggest that cholesterol may modulate ion channels by changing the levels of PIP2. Thus, an important cross-talk exists among two plasma membrane-enriched lipids, cholesterol and PIP2.Journal of Neurochemistry 12/2009; 112(5):1286-94. · 4.06 Impact Factor -
Article: Regulation of somatodendritic dopamine release by corticotropin-releasing factor via the inhibition of voltage-operated Ca2+ channels.
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ABSTRACT: Dopamine (DA) neurons in the substantia nigra pars compacta release DA from their somata and dendrites, which regulate motor activity and muscle tone. Previously, we reported that Ca(2+) influx through voltage-operated Ca(2+) channels (VOCCs) contributes to spontaneous somatodendritic DA release. Since corticotropin-releasing factor (CRF) regulates VOCC, we sought to determine whether urocortin affects somatodendritic DA release in the isolated DA neurons using amperometry method. The application of urocortin reversibly inhibited both VOCC and the frequency of DA release events via the activation of type-1 CRF receptor. The blockers for L- and T-type Ca(2+) channels effectively abolished the effects of urocortin both on the frequency of DA release events and on Ca(2+) current. These results indicate that CRF inhibits somatodendritic DA release by inhibiting L- and T-type Ca(2+) channels. Thus, the inhibition of somatodendritic DA release by stress hormone may be one of the molecular mechanisms underlying the effect of stress on motor function.Neuroscience Letters 10/2009; 465(1):31-5. · 2.11 Impact Factor -
Article: Voltage-operated Ca2+ channels regulate dopamine release from somata of dopamine neurons in the substantia nigra pars compacta.
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ABSTRACT: Dopamine (DA) neurons release DA not only from axon terminals at the striatum, but from their somata and dendrites at the substantia nigra pars compacta (SNc). Released DA may auto-regulate further DA release or modulate non-DA cells. However, the actual mechanism of somatodendritic DA release, especially the Ca(2+) dependency of the process, remains controversial. In this study, we used amperometry to monitor DA release from somata of acutely isolated rat DA neurons. We found that DA neurons spontaneously released DA in the resting state. Removal of extracellular Ca(2+) and application of blockers for voltage-operated Ca(2+) channels (VOCCs) suppressed the frequency of secretion events. Activation of VOCCs by stimulation with K(+)-rich saline increased the frequency of secretion events, which were also sensitive to blockers for L- and T-type Ca(2+) channels. These results suggest that Ca(2+) influx through VOCCs regulates DA release from somata of DA neurons.Biochemical and Biophysical Research Communications 08/2008; 373(4):665-9. · 2.48 Impact Factor -
Article: Involvement of corticotropin-releasing factor receptor 2 beta in differentiation of dopaminergic MN9D cells.
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ABSTRACT: Corticotropin releasing factor (CRF) mediates various responses to stress through CRF receptors 1 and 2. CRF receptor 2 has two forms, 2alpha and 2beta each of which appears to have distinct roles. Here we used dopaminergic neuron-derived MN9D cells to investigate the function of CRF receptor 2 in dopamine neurons. We found that n-butyrate, a histone deacetylase inhibitor, induced MN9D cell differentiation and increased gene expression of all CRF receptors. CRF receptor 2beta was minimally expressed in MN9D cells; however, its expression dramatically increased during differentiation. CRF receptor 2beta expression levels appeared to correlate with neurite outgrowth, suggesting CRF receptor 2beta involvement in neuronal differentiation. To validate this statement, we made a CRF receptor 2beta-overexpressing MN9D/CRFR2 beta stable cell line. This cell line showed robust neurite outgrowth and GAP43 overexpression, together with MEK and ERK activation, suggesting MN9D cell neuronal differentiation. From these results, we conclude that CRF receptor 2beta plays an important role in MN9D cell differentiation by activating the MEK/ERK signaling pathway.Molecules and Cells 06/2008; 26(3):243-9. · 2.18 Impact Factor -
Article: The endoplasmic reticulum as an integrator of multiple dendritic events.
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ABSTRACT: Dendrites are integrating elements that receive numerous subsets of heterogeneous synaptic inputs, which generate temporally and spatially distinct changes in membrane potential and intracellular Ca2+ levels in local domains. The ubiquitously distributed endoplasmic reticulum (ER) in dendrites is luminally connected to the bulk ER in the soma, constituting a huge interconnected intracellular network that allows rapid Ca2+ diffusion and equilibration. The ER is an excitable organelle that can elicit or terminate cytosolic Ca2+ signals in local or global domains. The absolute level or changes in the Ca2+ concentration in the ER lumen are also very important for the synthesis and maturation of proteins, regulation of gene expression, mitochondrial functions, neuronal excitability, and synaptic plasticity. Through the connected lumen of the ER, information from multiple dendritic events in neurons appears to be delivered into the bulk ER in the soma. Therefore, the ER network in neurons is emerging as a conveyor and integrator of signals. In this article, we will discuss the various roles of the ER and the functional and structural organization of the ER network in neurons.The Neuroscientist 03/2008; 14(1):68-77. · 4.57 Impact Factor -
Article: Nonselective cation channels are essential for maintaining intracellular Ca2+ levels and spontaneous firing activity in the midbrain dopamine neurons.
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ABSTRACT: Intracellular Ca2+ and Ca2+-permeable ion channels are important in regulating the firing activity and pattern of midbrain dopamine neurons, but the role of Ca2+-permeable nonselective cation channels (NSCCs) on spontaneous firing activity is unclear. Therefore, we investigated how Ca2+-permeable NSCCs modulate spontaneous firing activity and cytosolic Ca2+ concentration ([Ca2+]c) in acutely isolated midbrain dopamine neurons of the rat. Applications of voltage-dependent Ca2+ channels antagonists failed to abolish spontaneous firing activity completely, but they decreased firing rate and [Ca2+]c. However, a blockade of NSCCs by 2-APB or SKF96365 more potently suppressed spontaneous firings with a depolarization of membrane potential and strong decreases in basal [Ca2+]c levels. The depolarization of membrane potentials was attenuated by intracellular dialysis with 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). NSCCs blockers inhibited oscillatory potentials and decreased basal [Ca2+]c in the presence of tetrodotoxin. Apamin, a small-conductance Ca2+-activated K+ channel inhibitor, depolarized membrane potentials and enhanced firing rates. From these data, we conclude that NSCCs not only make up the tonic Ca2+ entry pathways to uphold basal [Ca2+]c levels but also contribute to generation of spontaneous firings, thereby regulating spontaneous firing activities of the midbrain dopamine neurons.Pflügers Archiv - European Journal of Physiology 12/2007; 455(2):309-21. · 4.46 Impact Factor -
Article: Modulation of T-type Ca2+ channels by corticotropin-releasing factor through protein kinase C pathway in MN9D dopaminergic cells.
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ABSTRACT: Corticotrophin-releasing factor (CRF) is the main regulator of the body's stress axis and its signal is translated through G-protein-coupled CRF receptors (CRF-R1, CRF-R2). Even though CRF receptors are present in the midbrain dopamine neurons, the cellular mechanism of CRF action is not clear yet. Since voltage-dependent Ca(2+) channels are highly expressed and important in dopamine neuronal functions, we tested the effect of CRF on voltage-dependent Ca(2+) channels in MN9D cells, a model of dopamine neurons. The application of CRF-related peptide, urocortin 1, reversibly inhibited T-type Ca(2+) currents, which was a major Ca(2+) channel in the cells. The effect of urocortin was abolished by specific CRF-R1 antagonist and was mimicked by protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate. PKC inhibitors abolished the effect of urocortin. These results suggest that urocortin modulates T-type Ca(2+) channel by interacting with CRF-R1 via the activation of PKC signal pathway in MN9D cells.Biochemical and Biophysical Research Communications 08/2007; 358(3):796-801. · 2.48 Impact Factor -
Article: Regional interaction of endoplasmic reticulum Ca2+ signals between soma and dendrites through rapid luminal Ca2+ diffusion.
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ABSTRACT: The endoplasmic reticulum (ER) Ca2+ store plays a key role in integration and conveyance of Ca2+ signals in highly polarized neurons. The interconnected ER network in neurons generates Ca2+ signals in local domains, but the regional interaction is unclear. Here, we show that continuous or repetitive applications of caffeine produced robust Ca2+ release from the ER Ca2+ store in dendritic areas without severe store depletion, but that similar stimuli applied to soma caused rapid store depletion in acutely isolated midbrain dopamine neurons. Partial emptying of the ER Ca2+ store within a dendrite caused a similar level of store depletion in unstimulated dendrites, as well as in soma. Photobleaching and local stimulation experiments revealed that Ca2+ and the dye trapped within the ER diffused rapidly from the soma to dendrites up to 90 microm, which we could resolve, suggesting that the ER network acts as a functional tunnel for rapid Ca2+ transport. These data imply that the ER in soma acts as a Ca2+ reservoir supplying Ca2+ to the dendritic store, and that the dendritic store, hence, is able to respond to Ca2+-mobilizing input signals endurably.Journal of Neuroscience 12/2006; 26(47):12127-36. · 7.11 Impact Factor -
Article: Regulation of zymogen granule exocytosis by Ca2+, cAMP, and PKC in pancreatic acinar cells.
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ABSTRACT: The effect of cAMP and PKC on zymogen granule exocytosis was investigated by simultaneously measuring cytosolic Ca2+ concentration ([Ca2+]c) and individual zymogen granule exocytosis in isolated mouse pancreatic acini. When acinar cells were stimulated with acetylcholine (ACh, 10 microM), exocytic events were detected through granule-attached apical membranes with [Ca2+]c rise. Application of secretin, forskolin (an adenylate cyclase activator), or PMA (a PKC activator) alone did not elicit any [Ca2+]c rise or zymogen granule exocytosis, but co-stimulation with ACh led to exocytosis in that the total number of secreted granules increased markedly without a significant difference in [Ca2+]c rises. When we evoked exocytosis by [Ca2+]c ramps, pretreatment with forskolin or PMA elicited exocytosis at lower [Ca2+]c levels. These results indicate that PKC or cAMP alone could not directly elicit zymogen granule exocytosis, but that they increase the total releasable pool by rendering zymogen granules more sensitive to Ca2+.Biochemical and Biophysical Research Communications 10/2005; 334(4):1241-7. · 2.48 Impact Factor -
Article: Endoplasmic reticulum Ca2+ store: regulation of Ca2+ release and reuptake by intracellular and extracellular Ca2+ in pancreatic acinar cells.
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ABSTRACT: We investigated the effect of cytosolic and extracellular Ca2+ on Ca2+ signals in pancreatic acinar cells by measuring Ca2+ concentration in the cytosol([Ca2+]c) and in the lumen of the ER([Ca2+]Lu). To control buffers and dye in the cytosol, a patch-clamp microelectrode was employed. Acetylcholine released Ca2+ mainly from the basolateral ER-rich part of the cell. The rate of Ca2+ release from the ER was highly sensitive to the buffering of [Ca2+]c whereas ER Ca2+ refilling was enhanced by supplying free Ca2+ to the cytosol with [Ca2+]c clamped at resting levels with a patch pipette containing 10 mM BAPTA and 2 mM Ca2+. Elevation of extracellular Ca2+ to 10 mM from 1 mM raised resting [Ca2+]c slightly and often generated [Ca2+]c oscillations in single or clustered cells. Although pancreatic acinar cells are reported to have extracellular Ca2+-sensing receptors linked to phospholipase C that mobilize Ca2+ from the ER, exposure of cells to 10 mM Ca2+ did not decrease [Ca2+]Lu but rather raised it. From these findings we conclude that 1) ER Ca2+ release is strictly regulated by feedback inhibition of [Ca2+]c, 2) ER Ca2+ refilling is determined by the rate of Ca2+ influx and occurs mainly in the tiny subplasmalemmal spaces, 3) extracellular Ca2+-induced [Ca2+]c oscillations appear to be triggered not by activation of extracellular Ca2+-sensing receptors but by the ER sensitised by elevated [Ca2+]c and [Ca2+]Lu.Molecules and Cells 05/2005; 19(2):268-78. · 2.18 Impact Factor -
Article: Two different Ca2+-dependent inhibitory mechanisms of spontaneous firing by glutamate in dopamine neurons.
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ABSTRACT: The excitatory neurotransmitter, glutamate, generates a characteristic burst-pause type of firing in midbrain dopamine neurons in association with the reward behavior, but the cellular mechanism by which glutamate generates these bursts is unknown. Here, we show that the bursts in spontaneously firing dopamine neurons can be generated by the combinative actions of the brief stimulatory and the subsequent Ca(2+)-dependent inhibitory signals in response to glutamate stimulation. The two Ca(2+)-dependent firing-extinction signals are activated by different glutamate receptors. Although the activation of metabotropic glutamate receptors rapidly stopped the enhanced firing through the Ca(2+) release from intracellular stores, the activation of NMDA and AMPA/kainate receptors abolished the firing immediately after termination of the stimulation due to the Ca(2+) accumulation in the cell. These two Ca(2+)-dependent inhibitory mechanisms appear to participate in the generation of characteristic bursts in dopamine neurons by controlling the maximum firing number of single bursts and the duration of post-firing pauses.Journal of Neurochemistry 12/2004; 91(4):983-95. · 4.06 Impact Factor -
Article: Morphological and functional changes of dissociated single pancreatic acinar cells: testing the suitability of the single cell as a model for exocytosis and calcium signaling.
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ABSTRACT: Isolated single pancreatic acinar cells have long been used as a model for studying many kinds of signaling processes due to their structural and functional polarities, but without significant validation. In this study, we examined the morphological and functional changes of dissociated single pancreatic acinar cells. Acutely isolated single cells showed a collapsed membrane potential and a much reduced secretion of zymogen granules in response to acetylcholine (ACh) stimulation, whereas clustered cells showed a much more negative membrane potential and potent exocytotic secretion. The isolated single cells became vertically flattened due to the loss of supporting adhesions with nearby cells, and the granule-attached luminal membrane was severely reduced versus that of clustered cells. However, polarized Ca(2+) signals and mitochondrial localizations were relatively well preserved in the isolated single cells, in that Ca(2+) release by ACh commenced at the indented luminal membrane. In clusters, the Ca(2+) release site was closest to the lumen where more than three cells met or at the tips of conical regions of the luminal membrane. These findings suggest that the dissociated single pancreatic acinar cells preserve an intact Ca(2+) signaling machinery but alter in shape and have impaired exocytotic functions and resting membrane potentials.Cell Calcium 05/2004; 35(4):367-79. · 3.77 Impact Factor -
Article: Glutamate-mediated [Ca2+]c dynamics in spontaneously firing dopamine neurons of the rat substantia nigra pars compacta.
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ABSTRACT: The mechanism by which glutamate regulates the cytosolic free Ca2+ concentration ([Ca2+]c) in spontaneously firing dopamine neurons is not clear. Thus we have investigated the glutamate-mediated [Ca2+]c dynamics in the acutely isolated dopamine neurons from the rat substantia nigra pars compacta by measuring [Ca2+]c and spontaneously occurring action potentials (SAPs). The freshly isolated dopamine neurons showed tetrodotoxin (TTX)-sensitive spontaneous firing of 2-3 Hz and the resting [Ca2+]c decreased with abolition of the SAPs. The level of [Ca2+]c was affected by the spontaneous firing rate. In the presence of the Na+ channel antagonist, TTX (0.5 microM), glutamate increased [Ca2+]c by activating different glutamate receptors depending on the glutamate concentration used. Addition of glutamate at low concentrations (<3 microM) raised [Ca2+]c mainly by activating metabotropic glutamate receptors (mGluR), whereas at high concentrations (>10 microM) it raised [Ca2+]c mainly by activating AMPA/kainate receptors. The contribution of NMDA receptors to the glutamate-mediated [Ca2+]c rises was largest at intermediate concentrations of glutamate. Activation of mGluR elicited a Ca2+ release from intracellular Ca2+ stores and continuous Ca2+ influx out of the cell. The spontaneous firing activities were highly enhanced by submicromolar levels of glutamate and abolished at levels above 10 microM. From these results, we conclude that at low glutamate concentrations the [Ca2+]c in the dopamine neurons is mainly governed by mGluR and the firing activities, whose rate is regulated at submicromolar glutamate concentrations, but at higher glutamate concentrations [Ca2+]c is dominantly affected by AMPA/kainate receptors.Journal of Cell Science 07/2003; 116(Pt 13):2665-75. · 6.11 Impact Factor -
Article: Low affinity cholecystokinin receptor inhibits cholecystokinin- and bombesin-induced oscillations of cytosolic Ca2+ concentration.
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ABSTRACT: We have investigated whether low affinity cholecystokinin (CCK) receptors suppress agonist-induced rises of cytosolic free Ca(2+) concentration ([Ca(2+)]c) in pancreatic acinar cells by using properties of caffeine. A high concentration of caffeine (20 mM) completely blocked inositol 1,4,5-trisphosphate (InsP(3))-induced [Ca(2+)]c rises but spared the InsP(3)-independent long-lasting [Ca(2+)]c oscillations. In the presence of 20 mM caffeine, only high concentrations of CCK, but not bombesin or JMV-180, suppressed the caffeine-resistant CCK or bombesin-induced [Ca(2+)]c oscillations, indicating that low affinity CCK receptors inhibit agonist-induced [Ca(2+)]c oscillations. It could be one of the underlying mechanisms by which low affinity CCK receptors suppress secretion in pancreatic acinar cells.FEBS Letters 04/2003; 538(1-3):134-8. · 3.54 Impact Factor
Top co-authors
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Institutions
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2005–2011
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Inje University Paik Hospital
Goyang, Gyeonggi, South Korea
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2002–2011
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Sungkyunkwan University
- Department of Physiology
Seoul, Seoul, South Korea
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