Expression of the L-Type Ca&lt;sup&gt;2+&lt;/sup&gt; Channel in AtT-20 Cells Is Regulated by Cyclic AMP

Xie, Jiangang; Nagle, Gregg T.; Childs, Gwen V.; Ritchie, A K

doi:10.1159/000054454

Cited by 15 publications

(6 citation statements)

References 37 publications

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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%

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%

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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“…Furthermore, since the value of the initial current density is reduced by half after a depolarization lasting 14 h, it is likely that the half-life of this subunit is within this time frame. This is consistent with the reported values of the half-life of the α subunit of neuronal L-type Ca 2+ channels [38] and of Na + channels [32].…”

Section: Mechanism Of Down-regulationsupporting

confidence: 93%

Long-term depolarization regulates the α 1s subunit of skeletal muscle Ca 2+ channels and the amplitude of L-type Ca 2+ currents

Escamilla

Farías

García

et al. 2001

Pfl�gers Archiv European Journal of Physiology

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The effects of long-term depolarization on the level of alpha1s and on L-type Ca2+ currents of skeletal muscle were investigated. Long-term depolarization (14 h) caused a 50% decrease of alpha1s, revealed with the Western blot technique. This decline was prevented by preincubation with the Ca2+ channel blocker nifedipine. Electrophysiological experiments using the voltage-clamp technique were performed to measure the actions of long-term depolarization on Ca2+ currents and charge movement. A progressive decline in the amplitude of the Ca2+ currents by depolarizations lasting 0.5-14 h was observed. Similar to Western blot results, the fall in current amplitude was prevented by nifedipine, and it depended on external Ca2+. The nonlinear charge mobilized by step pulses was also significantly reduced (50%) by long-term depolarization. It is suggested that alpha1s subunit is down-regulated by long-term depolarization by a very stringent mechanism and that, in this process, Ca2+ ions permeating through L-type channels play a key role. A new role for the L-type Ca2+ current in skeletal muscle fibers in which the channels are self-regulated is proposed.

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“…Rapid PKA-mediated phosphorylation of L-type Ca v channels has not been studied but should not be excluded. However, cAMP stimulates the expression of the L-type Ca v channels in AtT-20 cells at the mRNA and protein levels, presumably through PKA (503). Corticotrophs also express T-type Ca v channels, but their role in CRH action has not been studied.…”

Section: Crh-induced Calcium Influx In Corticotrophsmentioning

confidence: 99%

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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Expression of the L-Type Ca<sup>2+</sup> Channel in AtT-20 Cells Is Regulated by Cyclic AMP

Cited by 15 publications

References 37 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

Long-term depolarization regulates the α 1s subunit of skeletal muscle Ca 2+ channels and the amplitude of L-type Ca 2+ currents

Ion Channels and Signaling in the Pituitary Gland

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