CRH-induced Electrical Activity and Calcium Signalling in Pituitary Corticotrophs

Shorten, Paul R.; Robson, Alexander B.; McKinnon, Alan E.; Wall, David J. N.

doi:10.1006/jtbi.2000.2135

Cited by 17 publications

(20 citation statements)

References 41 publications

(69 reference statements)

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“…To this point, our data are in agreement with published reports showing that CRH induces calcium ion entrance from extra-cellular 2,5,[15][16][17][18] and/or intra-cellular sources 3,6,7,15,16,19,20 .…”

Section: Discussionsupporting

confidence: 93%

“…The inhibitor of PKC phosphorylation, the pseudo-substrate myristoylated alanine-rich PKC [20][21][22][23][24][25][26][27][28] (Myr-N-FARK-GALRQ-NH 2 ) and the inhibitor of PKA phosphorylation, myristoylated PKA [14][15][16][17][18][19][20][21][22] (Myr-GRTGR-RNAI-NH2) were obtained from Calbiochem (La Jolla, CA) while the activator of conventional and novel PKC isoenzymes, phorbol 12-myristate 13-ace-…”

Section: Reagents and Antibodiesmentioning

confidence: 99%

“…Figure 1, panel A depicts the effect of CRH at 1 nM which induced an acute elevation of cytosolic calcium ions. Figure 1, panel D depicts the effect of the simultaneous presence of the PKA phosphorylation inhibitor myristoylated PKA [14][15][16][17][18][19][20][21][22] at 100 ìÌ on CRH-induced calcium ion elevation in PC12 cells in a calcium rich environment. Indeed, the PKA inhibitor prevented the stimulatory effect of CRH suggesting that PKA-dependent signalling pathways mediate its effect.…”

Section: Effect Of Crh ± Pka or Pkc Inhibitors On Calcium Ion Influxmentioning

confidence: 99%

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Roles of Protein Kinase A (PKA) and PKC on Corticotropin-Releasing Hormone (CRH)-Induced Elevation of Cytosolic Calcium from Extra- and Intra-cellular Sources

Dermitzaki¹,

Tsatsanis²,

Alexaki³

et al. 2004

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Corticotropin-releasing hormone (CRH) affects cytosolic calcium ion levels. The aim of the present work was to examine the role of protein kinase A (PKA)-and PKC-dependent signalling pathways in mediating the effect of CRH on calcium ion influx (from extra-cellular sources) and calcium ion mobilization (from intra-cellular stores). In this study, we employed a well-known model of neural crest-derived cells, the PC12 rat pheochromocytoma cell line. We found that CRH increased the concentration of cytosolic calcium ions in calcium-rich and in calcium-free media. In both conditions, an inhibitor of PKA phosphorylation abolished the effect of CRH. In contrast, the inhibitor of PKC phosphorylation blocked the effect of CRH only in calcium-free conditions. The phorbol ester PMA, activator of PKC, accelerated the steep of the curve of cytosolic calcium ion increase from intracellular stores. These data suggest that: (a) CRH induces calcium ion entrance into the cytoplasm from both extra-cellular sources (influx) and from intra-cellular stores (mobilization); (b) the PKAdependent signalling pathway mediates both effects of CRH; and (c) the PKC-dependent signalling pathway mediates only the CRH-induced mobilization of calcium ions from intra-cellular stores. Thus, this is the first report demonstrating that distinct signalling pathways control the effects of CRH on calcium ion influx and on calcium ion mobilization from intra-cellular stores. in the hippocampus 5,9-11 . Furthermore, it has been shown that in human epidermoid cells, CRH induces the activity as well as the translocation of PKC isoenzymes 12 . Finally, exposure of neuroblastoma cells to phorbol esters, activators of PKC, results in up-regulation of CRH binding sites suggesting an additional mechanism through which the PKC signalling pathway may modulate some of the biological effects of CRH 13 .Based on the data mentioned above, it has been hypothesized that the effect of CRH on cytosolic calcium ion levels may be mediated by either the PKA or the PKC signalling pathways. It should be noted that a recent report states that this may be true for the skin 14 . Indeed, in corticotroph cells, although PKA mediated the stimulatory effect of dBcAMP and forskolin on calcium ion influx (through voltage-gated Ca ion channels), it only partially mediated the effect of CRH, giving the impression that the effect of CRH on calcium ion influx may be also mediated by a cAMP-independent mechanism 5,15 . Thus, it has been proposed that CRH stimulates calcium ion influx, mainly via L-type Ca ion channels. The observed calcium ion influx, which is independent of action potentials (membrane depolarization) and mediated by PKC, may involve P-type calcium ion channels 16 .The aim of the present work was to elucidate the role of the PKA and PKC signalling pathways in the mediation of the stimulatory effect of CRH on cytosolic ion levels from extra-cellular and intra-cellular calcium ion sources. In this study, we employed a wellknown model of neural crest-derived cells, th...

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Section: Discussionsupporting

confidence: 93%

Section: Reagents and Antibodiesmentioning

confidence: 99%

Section: Effect Of Crh ± Pka or Pkc Inhibitors On Calcium Ion Influxmentioning

confidence: 99%

See 1 more Smart Citation

Roles of Protein Kinase A (PKA) and PKC on Corticotropin-Releasing Hormone (CRH)-Induced Elevation of Cytosolic Calcium from Extra- and Intra-cellular Sources

Dermitzaki¹,

Tsatsanis²,

Alexaki³

et al. 2004

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show abstract

“…A mathematical model of the corticotroph confirms that depolarization induced by blocking a background K ϩ current facilitates spiking but cannot by itself trigger AP firing (501). On the other hand, facilitation of the L-type Ca v current is sufficient for the model to generate spikes or bursts (501,761). However, there is no evidence that CRH receptor activation leads to phosphorylation of these channels by PKA, as in other cell types.…”

Section: Crh-induced Calcium Influx In Corticotrophsmentioning

confidence: 87%

Ion Channels and Signaling in the Pituitary Gland

2010

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Endocrine pituitary cells are neuronlike; they express numerous voltage-gated sodium, calcium, potassium, and chloride channels and fire action potentials spontaneously, accompanied by a rise in intracellular calcium. In some cells, spontaneous electrical activity is sufficient to drive the intracellular calcium concentration above the threshold for stimulus-secretion and stimulus-transcription coupling. In others, the function of these action potentials is to maintain the cells in a responsive state with cytosolic calcium near, but below, the threshold level. Some pituitary cells also express gap junction channels, which could be used for intercellular Ca(2+) signaling in these cells. Endocrine cells also express extracellular ligand-gated ion channels, and their activation by hypothalamic and intrapituitary hormones leads to amplification of the pacemaking activity and facilitation of calcium influx and hormone release. These cells also express numerous G protein-coupled receptors, which can stimulate or silence electrical activity and action potential-dependent calcium influx and hormone release. Other members of this receptor family can activate calcium channels in the endoplasmic reticulum, leading to a cell type-specific modulation of electrical activity. This review summarizes recent findings in this field and our current understanding of the complex relationship between voltage-gated ion channels, ligand-gated ion channels, gap junction channels, and G protein-coupled receptors in pituitary cells.

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“…Figure 1A shows an example from a pituitary lactotroph cell line (GH4 cell). Mathematical models for bursting in lactotrophs (Tabak et al , 2007; Toporikova et al , 2008), somatotrophs (Tsaneva-Atanasova et al , 2007), corticotrophs (LeBeau et al , 1998; Shorten et al , 2000), and single β -cells (Zhang et al , 2003) have been developed and analyzed. This type of bursting, called “pseudo-plateau” bursting, is quite different from that of most neurons and neuron models, as discussed in Stern et al (2008).…”

Section: Introductionmentioning

confidence: 99%

Mixed mode oscillations as a mechanism for pseudo-plateau bursting

Bertram

Tabak

et al. 2010

J Comput Neurosci

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We combine bifurcation analysis with the theory of canard-induced mixed mode oscillations to investigate the dynamics of a novel form of bursting. This bursting oscillation, which arises from a model of the electrical activity of a pituitary cell, is characterized by small impulses or spikes riding on top of an elevated voltage plateau. Oscillations with these characteristics have been called “pseudo-plateau bursting”. Unlike standard bursting, the subsystem of fast variables does not posses a stable branch of periodic spiking solutions, and in the case studied here the standard fast/slow analysis provides little information about the underlying dynamics. We demonstrate that the bursting is actually a canard-induced mixed mode oscillation, and use canard theory to characterize the dynamics of the oscillation. We also use bifurcation analysis of the full system of equations to extend the results of the singular analysis to the physiological regime. This demonstrates that the combination of these two analysis techniques can be a powerful tool for understanding the pseudo-plateau bursting oscillations that arise in electrically excitable pituitary cells and isolated pancreatic β-cells.

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CRH-induced Electrical Activity and Calcium Signalling in Pituitary Corticotrophs

Cited by 17 publications

References 41 publications

Roles of Protein Kinase A (PKA) and PKC on Corticotropin-Releasing Hormone (CRH)-Induced Elevation of Cytosolic Calcium from Extra- and Intra-cellular Sources

Roles of Protein Kinase A (PKA) and PKC on Corticotropin-Releasing Hormone (CRH)-Induced Elevation of Cytosolic Calcium from Extra- and Intra-cellular Sources

Ion Channels and Signaling in the Pituitary Gland

Mixed mode oscillations as a mechanism for pseudo-plateau bursting

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