Modulation of T-type Ca2+ channels by corticotropin-releasing factor through protein kinase C pathway in MN9D dopaminergic cells

Kim, Yonjung; Park, Myoung Kyu; Uhm, Dae-Yong; Chung, Sungkwon

doi:10.1016/j.bbrc.2007.04.198

Cited by 21 publications

(13 citation statements)

References 29 publications

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“…2). This conclusion is consistent with previous reports for PKCmediated modulation of Ca V channels (e.g., Sculptoreanu and de Groat, 2003;Kim et al, 2007). Several putative PKC consensus motifs localize to the II-III linker in Ca V 3 channels (Monteil et al, 2000), which could be involved in their regulation by this enzyme .…”

Section: Nk1 Receptor Modulates Ca V 32 207supporting

confidence: 93%

“…It has been shown previously that T-type Ca V 3.2 channels are modulated by several different types of heterotrimeric G protein-coupled receptors (Welsby et al, 2003;Wolfe et al, 2003;Kim et al, 2006Kim et al, , 2007Iftinca et al, 2007;Tao et al, 2008). However, little is currently known regarding the modulation of T-type channels by tachykinin receptors.…”

Section: Resultsmentioning

confidence: 99%

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Protein Kinase C-Mediated Inhibition of Recombinant T-Type Ca_V3.2 Channels by Neurokinin 1 Receptors

Rangel¹,

Sánchez‐Armass²,

Meza³

2009

Mol Pharmacol

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The voltage-activated T-type calcium channel (Ca V 3.2) and the G protein-coupled neurokinin 1 (NK1) receptor are expressed in peripheral tissues and in central neurons, in which they participate in diverse physiological processes, including neurogenic inflammation and nociception. In the present report, we demonstrate that recombinant Ca V 3.2 channels are reversibly inhibited by NK1 receptors when both proteins are transiently coexpressed in human embryonic kidney 293 cells. We found that the voltage-dependent macroscopic properties of Ca V 3.2 currents were unaffected during NK1 receptor-mediated inhibition. However, inhibition was attenuated in cells coexpressing either the dominant-negative G␣ q Q209L/D277N or the regulator of G protein signaling (RGS) proteins 2 (RGS2) and 3T (RGS3T), which are effective antagonists of G␣ q/11 . By contrast, inhibition was unaffected in cells coexpressing human rod transducin (G␣ t ), which buffers G␤␥. Channel inhibition was blocked by 1-[6-[[17␤-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122) and bisindolylmaleimide I, selective inhibitors of phospholipase C␤ and protein kinase C (PKC), respectively. Inhibition was occluded by application of the PKC activator phorbol-12-myristate-13-acetate. Altogether, these data indicate that NK1 receptors inhibit Ca V 3.2 channels through a voltage-independent signaling pathway that involves G␣ q/11 , phospholipase C␤, and PKC. Our results provide novel evidence regarding the mechanisms underlying T-type calcium channel modulation by G protein-coupled receptors. Functional coupling between Ca V 3.2 channels and NK1 receptors may be relevant in neurogenic inflammation, neuronal rhythmogenesis, nociception, and other physiological processes.

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Section: Nk1 Receptor Modulates Ca V 32 207supporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Protein Kinase C-Mediated Inhibition of Recombinant T-Type Ca_V3.2 Channels by Neurokinin 1 Receptors

Rangel¹,

Sánchez‐Armass²,

Meza³

2009

Mol Pharmacol

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“…Therefore, it is possible that T-type VGCCs represent another mode of ROC entry that is sensitive to PKC activation. Consistent with this hypothesis are multiple findings (Park et al, 2003(Park et al, , 2006Chemin et al, 2007;Kim et al, 2007) illustrating that PKC activation stimulates Ca v 3.1 and Ca v 3.2 Ca 2ϩ currents. Although the specific PKC isoforms modulating Ca 2ϩ influx through T-type VGCCs were not determined in those prior reports, our data suggest that PKC ε plays a role in stimulating Ca 2ϩ influx in the pulmonary endothelium.…”

Section: Discussionmentioning

confidence: 57%

Altered Protein Kinase C Regulation of Pulmonary Endothelial Store- and Receptor-Operated Ca²⁺Entry after Chronic Hypoxia

Paffett¹,

Riddle²,

Kanagy³

et al. 2010

J Pharmacol Exp Ther

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Chronic hypoxia (CH)-induced pulmonary hypertension is associated with decreased basal pulmonary artery endothelial cell (EC) Ca 2ϩ , which correlates with reduced storeoperated Ca 2ϩ (SOC) entry. Protein kinase C (PKC) attenuates SOC entry in ECs. Therefore, we hypothesized that PKC has a greater inhibitory effect on EC SOC and receptoroperated Ca 2ϩ entry after CH. To test this hypothesis, we assessed SOC in the presence or absence of the nonselec-in freshly isolated, Fura-2-loaded ECs obtained from intrapulmonary arteries of control and CH rats (4 weeks at 0.5 atm). We found that SOC entry and 1-oleoyl-2-acetyl-sn-glycerol (OAG)-and ATP-induced Ca 2ϩ influx were attenuated in ECs from CH rats versus controls, and GF109203X restored SOC and OAG responses to the level of controls. In contrast, nonselective PKC inhibition with GF109203X or the selective PKC inhibitor myristoylated V1-2 attenuated ATP-induced Ca 2ϩ entry in ECs from control but not CH pulmonary arteries. ATP-induced Ca 2ϩ entry was also attenuated by the T-type voltage-gated Ca 2ϩ channel (VGCC) inhibitor mibefradil in control cells. Consistent with the presence of endothelial T-type VGCC, we observed depolarization-induced Ca 2ϩ influx in control cells that was inhibited by mibefradil. This response was largely absent in ECs from CH arteries. We conclude that CH enhances PKC-dependent inhibition of SOC-and OAG-induced Ca 2ϩ entry. Furthermore, these data suggest that CH may reduce the ATP-dependent Ca 2ϩ entry that is mediated, in part, by PKC and mibefradil-sensitive Ca 2ϩ channels in control cells.

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“…Although the electrophysiological properties of Ca V 3 T-type channels are primarily regulated by dynamic changes in membrane potential, their functional properties can also be modulated by the actions of hormones or neurotransmitters acting via GPCRs that trigger downstream transduction pathways (Welsby et al, 2003;Wolfe et al, 2003;Chemin et al, 2006;Kim et al, 2006). UCN, an endogenous agonist for CRF receptors, has been shown to either attenuate or stimulate low threshold calcium currents depending on the type of native cells examined (Lee and Tse, 1997;Tao et al, 2005;Kim et al, 2007). Various T-type calcium channel subtypes are expressed in these cells (Jagannathan et al, 2002); however, because of the lack of discriminatory antagonists, the selective inhibitory effect of CRFR1 activation on each of the three Ca V 3 channels-Ca V 3.1, Ca V 3.2, and Ca V 3.3-could not be investigated pharmacologically in these cells.…”

mentioning

confidence: 99%

Activation of Corticotropin-Releasing Factor Receptor 1 Selectively Inhibits Ca_V3.2 T-Type Calcium Channels

Tao

Hildebrand²,

Liao³

et al. 2008

Mol Pharmacol

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The corticotropin-releasing factor (CRF) peptides CRF and urocortins 1 to 3 are crucial regulators of mammalian stress and inflammatory responses, and they are also implicated in disorders such as anxiety, depression, and drug addiction. There is considerable interest in the physiological mechanisms by which CRF receptors mediate their widespread effects, and here we report that the native CRF receptor 1 (CRFR1) endogenous to the human embryonic kidney 293 cells can functionally couple to mammalian Ca V 3.2 T-type calcium channels. Activation of CRFR1 by either CRF or urocortin (UCN) 1 reversibly inhibits Ca V 3.2 currents (IC 50 of ϳ30 nM), but it does not affect Ca V 3.1 or Ca V 3.3 channels. Blockade of CRFR1 by the antagonist astressin abolished the inhibition of Ca V 3.2 channels. The CRFR1-dependent inhibition of Ca V 3.2 channels was independent of the activities of phospholipase C, tyrosine kinases, Ca 2ϩ /calmodulin-dependent protein kinase II, protein kinase C, and other kinase pathways, but it was dependent upon a cholera toxin-sensitive G protein-mediated mechanism relying upon G protein ␤␥ subunits (G␤␥). The inhibition of Ca V 3.2 channels via the activation of CRFR1 was due to a hyperpolarized shift in their steady-state inactivation, and it was reversible upon washout of the agonists. Given that UCN affect multiple aspects of cardiac and neuronal physiology and that Ca V 3.2 channels are widespread throughout the cardiovascular and nervous systems, the results point to a novel and functionally relevant CRFR1-Ca V 3.2 T-type calcium channel signaling pathway.The corticotropin-releasing factor (CRF) family, consisting of CRF, urocortin 1 (UCN), UCN2, and UCN3, are critical regulators of stress and inflammatory responses, and they have been variously associated with being cardioprotective and contributing toward alcohol and drug dependencies (Reul and Holsboer, 2002;Bale and Vale, 2004;Bruijnzeel and Gold, 2005;Gravanis and Margioris, 2005). The two major receptors for CRF and UCNs, CRF receptor (CRFR)1 and CRFR2, have been identified as G protein-coupled receptors (GPCRs) that can mediate responses via activation of the protein kinase signaling pathways (Bruijnzeel and Gold, 2005;Gravanis and Margioris, 2005). CRF has a higher affinity for CRFR1 than for CRFR2, UCN shows high affinity for both CRFR1 and CRFR2, whereas UCN2 and UCN3 are selective for CRFR2 (Bale and Vale, 2004). The CRFR1 is expressed primarily in the brain and pituitary, and activation of CRFR1 exerts numerous central and peripheral effects associated with pathological diseases (Dautzenberg and Hauger, 2002). Within the hypothalamus-pituitary axis, CRF and CRF-related peptides such as UCN activate CRFR1 receptors to regulate pituitary function in response to stress T.W

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Modulation of T-type Ca2+ channels by corticotropin-releasing factor through protein kinase C pathway in MN9D dopaminergic cells

Cited by 21 publications

References 29 publications

Protein Kinase C-Mediated Inhibition of Recombinant T-Type Ca_V3.2 Channels by Neurokinin 1 Receptors

Protein Kinase C-Mediated Inhibition of Recombinant T-Type Ca_V3.2 Channels by Neurokinin 1 Receptors

Altered Protein Kinase C Regulation of Pulmonary Endothelial Store- and Receptor-Operated Ca²⁺Entry after Chronic Hypoxia

Activation of Corticotropin-Releasing Factor Receptor 1 Selectively Inhibits Ca_V3.2 T-Type Calcium Channels

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Modulation of T-type Ca2+ channels by corticotropin-releasing factor through protein kinase C pathway in MN9D dopaminergic cells

Cited by 21 publications

References 29 publications

Protein Kinase C-Mediated Inhibition of Recombinant T-Type CaV3.2 Channels by Neurokinin 1 Receptors

Protein Kinase C-Mediated Inhibition of Recombinant T-Type CaV3.2 Channels by Neurokinin 1 Receptors

Altered Protein Kinase C Regulation of Pulmonary Endothelial Store- and Receptor-Operated Ca2+Entry after Chronic Hypoxia

Activation of Corticotropin-Releasing Factor Receptor 1 Selectively Inhibits CaV3.2 T-Type Calcium Channels

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Product

Resources

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Protein Kinase C-Mediated Inhibition of Recombinant T-Type Ca_V3.2 Channels by Neurokinin 1 Receptors

Protein Kinase C-Mediated Inhibition of Recombinant T-Type Ca_V3.2 Channels by Neurokinin 1 Receptors

Altered Protein Kinase C Regulation of Pulmonary Endothelial Store- and Receptor-Operated Ca²⁺Entry after Chronic Hypoxia

Activation of Corticotropin-Releasing Factor Receptor 1 Selectively Inhibits Ca_V3.2 T-Type Calcium Channels