ORCID Profile
0000-0001-5806-0207
Current Organisation
University of Leeds
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Publisher: Society for Neuroscience
Date: 03-04-2013
DOI: 10.1523/JNEUROSCI.4275-12.2013
Abstract: We have identified a new signaling role for nitric oxide (NO) in neurons from the trigeminal ganglia (TG). We show that in rat sensory neurons from the TG the NO donor, S -nitroso- N -acetyl- d l -penicillamine, inhibited M-current. This inhibitory effect was blocked by NO scavenging, while inhibition of NO synthases increased M-current, suggesting that tonic NO levels inhibit M-current in TG neurons. Moreover NO increased neuronal excitability and calcitonin gene-related peptide (CGRP) release and these effects could be prevented by perturbing M-channel function. First, NO-induced depolarization was prevented by pre-application of the M-channel blocker XE991 and second, NO-induced increase in CGRP release was prevented by incubation with the M-channel opener retigabine. We investigated the mechanism of the effects of NO on M-channels and identified a site of action of NO to be the redox modulatory site at the triplet of cysteines within the cytosolic linker between transmembrane domains 2 and 3, which is also a site of oxidative modification of M-channels by reactive oxygen species (ROS). NO and oxidative modifications have opposing effects on M-current, suggesting that a tightly controlled local redox and NO environment will exert fine control over M-channel activity and thus neuronal excitability. Together our data have identified a dynamic redox sensor within neuronal M-channels, which mediates reciprocal regulation of channel activity by NO and ROS. This sensor may play an important role in mediating excitatory effects of NO in such trigeminal disorders as headache and migraine.
Publisher: Springer Science and Business Media LLC
Date: 02-2009
Publisher: Mary Ann Liebert Inc
Date: 20-02-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2011
Publisher: Elsevier BV
Date: 10-2001
DOI: 10.1016/S1095-6433(01)00422-6
Abstract: Ample pharmacological evidence points to a role of kinases in the regulation of cell volume. Given the limited selectivity of most inhibitors, however, the specific molecules involved have remained largely elusive. The search for cell volume regulated genes in liver HepG2 cells led to the discovery of the human serum- and glucocorticoid-dependent serine/threonine kinase hsgk1. Transcription and expression of hsgk1 is markedly and rapidly upregulated by osmotic and isotonic cell shrinkage. The effect of osmotic cell shrinkage on hsgk1 is mediated by p38 kinase. Further stimuli of hsgk1 transcription include glucocorticoids, aldosterone, TGF-beta1, serum, increase of intracellular Ca2+ and phorbolesters, whereas cAMP downregulates hsgk1 transcription. The hsgk1 protein is expressed in several epithelial tissues including human pancreas, intestine, kidney, and shark rectal gland. Co-expression of hsgk1 with the renal epithelial Na+-channel ENaC or the Na+/K+/2Cl(-)-cotransporter NKCC2 (BSC1) in Xenopus oocytes, accelerates insertion of the transport proteins into the cell membrane and thus, stimulates channel or transport activity. Thus, hsgk1 participates in the regulation of transport by steroids and secretagogues increasing intracellular Ca2+-activity. The stimulation of hsgk1 transcription by TGF-beta1 may further bear pathophysiological relevance.
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
Location: Russian Federation
No related grants have been discovered for Nikita Gamper.