Chronic Nicotine Modifies Skeletal Muscle Na,K-ATPase Activity through Its Interaction with the Nicotinic Acetylcholine Receptor and Phospholemman

Our previous finding that the muscle nicotinic acetylcholine receptor (nAChR) and the Na,K-ATPase interact as a regulatory complex to modulate Na,K-ATPase activity suggested that chronic, circulating nicotine may alter this interaction, with long-term changes in the membrane potential. To test this hypothesis, we chronically exposed rats to nicotine delivered orally for 21–31 days. Chronic nicotine produced a steady membrane depolarization of ∼3 mV in the diaphragm muscle, which resulted from a net change in electrogenic transport by the Na,K-ATPase α2 and α1 isoforms. Electrogenic transport by the α2 isoform increased (+1.8 mV) while the activity of the α1 isoform decreased (−4.4 mV). Protein expression of Na,K-ATPase α1 or α2 isoforms and the nAChR did not change; however, the content of α2 subunit in the plasma membrane decreased by 25%, indicating that its stimulated electrogenic transport is due to an increase in specific activity. The physical association between the nAChR, the Na,K-ATPase α1 or α2 subunits, and the regulatory subunit of the Na,K-ATPase, phospholemman (PLM), measured by co-immuno precipitation, was stable and unchanged. Chronic nicotine treatment activated PKCα/β2 and PKCδ and was accompanied by parallel increases in PLM phosphorylation at Ser63 and Ser68. Collectively, these results demonstrate that nicotine at chronic doses, acting through the nAChR-Na,K-ATPase complex, is able to modulate Na,K-ATPase activity in an isoform-specific manner and that the regulatory range includes both stimulation and inhibition of enzyme activity. Cholinergic modulation of Na,K-ATPase activity is achieved, in part, through activation of PKC and phosphorylation of PLM

Contrôle de l' expression apicale du co-transporteur NKCC2 (rôle des interactions protéine-protéine)

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Resources for the renal physiome

International audienceThe Quantitative Kidney Database (QKDB, http://www.lami.univ-evry.fr/srthomas/qkdb/) is accessible to all for consultation and is open to the renal research community for (password protected) data entry. It contains, for human kidneys where known, but especially in experimentally studied species (mammalian, amphibian, avian, ) and in model epithelia such as cultured cells and amphibian skin and urinary bladder: transport parameters (permeabilities to water and solutes, kinetics of transporters and channels, in all nephron and vessel segments and kidney regions); tubular concentrations and flow rates along nephrons and vessels; qualitative and quantitative anatomical details (e.g., tubule diameters and epithelial and cellular dimensions; relative placement of structures in each kidney region; and typical kidney sizes and weights for different species; dimensions of cortical and medullary regions and subregions). In this presentation, we demonstrate our recent extensions to QKDB allowing inclusion of a wider range of content, in particular, time series (e.g., data on tubulo-glomerular feedback), images (e.g., anatomical), equations (in MathML) for channel and transporter kinetics, and videos. We have added functional links to other renal databases (such as the collecting duct database, CDDB, and the Rat Genome Database, RGD) and ontologies. We also report recent progress on standardization of terminology (i.e., ontologies), including renal anatomy and parameter descriptors

Vers un entrepôt de données XML pour le Physiome rénal

Vers un entrepôt de données XML pour le Physiome réna

Vers un physiome XML pour le Physiome rénal

Vers un physiome XML pour le Physiome réna