The Role of the Membrane Potential in Chondrocyte Volume Regulation

Many cell types have significant negative resting membrane potentials (RMPs) resulting from the activity of potassium-selective and chloride-selective ion channels. In excitable cells, such as neurones, rapid changes in membrane permeability underlie the generation of action potentials. Chondrocytes...

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Main Authors:	Lewis, Rebecca, Asplin, Katie E, Bruce, Gareth, Dart, Caroline, Mobasheri, Ali, Barrett-Jolley, Richard
Format:	Online
Language:	English
Published:	Wiley Subscription Services, Inc., A Wiley Company 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229839/

id	pubmed-3229839
recordtype	oai_dc
spelling	pubmed-32298392011-12-05 The Role of the Membrane Potential in Chondrocyte Volume Regulation Lewis, Rebecca Asplin, Katie E Bruce, Gareth Dart, Caroline Mobasheri, Ali Barrett-Jolley, Richard Original Research Article Many cell types have significant negative resting membrane potentials (RMPs) resulting from the activity of potassium-selective and chloride-selective ion channels. In excitable cells, such as neurones, rapid changes in membrane permeability underlie the generation of action potentials. Chondrocytes have less negative RMPs and the role of the RMP is not clear. Here we examine the basis of the chondrocyte RMP and possible physiological benefits. We demonstrate that maintenance of the chondrocyte RMP involves gadolinium-sensitive cation channels. Pharmacological inhibition of these channels causes the RMP to become more negative (100 µM gadolinium: ΔVm = −30 ± 4 mV). Analysis of the gadolinium-sensitive conductance reveals a high permeability to calcium ions (PCa/PNa ≈80) with little selectivity between monovalent ions; similar to that reported elsewhere for TRPV5. Detection of TRPV5 by PCR and immunohistochemistry and the sensitivity of the RMP to the TRPV5 inhibitor econazole (ΔVm = −18 ± 3 mV) suggests that the RMP may be, in part, controlled by TRPV5. We investigated the physiological advantage of the relatively positive RMP using a mathematical model in which membrane stretch activates potassium channels allowing potassium efflux to oppose osmotic water uptake. At very negative RMP potassium efflux is negligible, but at more positive RMP it is sufficient to limit volume increase. In support of our model, cells clamped at −80 mV and challenged with a reduced osmotic potential swelled approximately twice as much as cells at +10 mV. The positive RMP may be a protective adaptation that allows chondrocytes to respond to the dramatic osmotic changes, with minimal changes in cell volume. J. Cell. Physiol. 226: 2979–2986, 2011. © 2011 Wiley-Liss, Inc. Wiley Subscription Services, Inc., A Wiley Company 2011-11 2011-02-15 /pmc/articles/PMC3229839/ /pubmed/21328349 http://dx.doi.org/10.1002/jcp.22646 Text en Copyright © 2011 Wiley-Liss, Inc., A Wiley Company http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Lewis, Rebecca Asplin, Katie E Bruce, Gareth Dart, Caroline Mobasheri, Ali Barrett-Jolley, Richard
spellingShingle	Lewis, Rebecca Asplin, Katie E Bruce, Gareth Dart, Caroline Mobasheri, Ali Barrett-Jolley, Richard The Role of the Membrane Potential in Chondrocyte Volume Regulation
author_facet	Lewis, Rebecca Asplin, Katie E Bruce, Gareth Dart, Caroline Mobasheri, Ali Barrett-Jolley, Richard
author_sort	Lewis, Rebecca
title	The Role of the Membrane Potential in Chondrocyte Volume Regulation
title_short	The Role of the Membrane Potential in Chondrocyte Volume Regulation
title_full	The Role of the Membrane Potential in Chondrocyte Volume Regulation
title_fullStr	The Role of the Membrane Potential in Chondrocyte Volume Regulation
title_full_unstemmed	The Role of the Membrane Potential in Chondrocyte Volume Regulation
title_sort	role of the membrane potential in chondrocyte volume regulation
description	Many cell types have significant negative resting membrane potentials (RMPs) resulting from the activity of potassium-selective and chloride-selective ion channels. In excitable cells, such as neurones, rapid changes in membrane permeability underlie the generation of action potentials. Chondrocytes have less negative RMPs and the role of the RMP is not clear. Here we examine the basis of the chondrocyte RMP and possible physiological benefits. We demonstrate that maintenance of the chondrocyte RMP involves gadolinium-sensitive cation channels. Pharmacological inhibition of these channels causes the RMP to become more negative (100 µM gadolinium: ΔVm = −30 ± 4 mV). Analysis of the gadolinium-sensitive conductance reveals a high permeability to calcium ions (PCa/PNa ≈80) with little selectivity between monovalent ions; similar to that reported elsewhere for TRPV5. Detection of TRPV5 by PCR and immunohistochemistry and the sensitivity of the RMP to the TRPV5 inhibitor econazole (ΔVm = −18 ± 3 mV) suggests that the RMP may be, in part, controlled by TRPV5. We investigated the physiological advantage of the relatively positive RMP using a mathematical model in which membrane stretch activates potassium channels allowing potassium efflux to oppose osmotic water uptake. At very negative RMP potassium efflux is negligible, but at more positive RMP it is sufficient to limit volume increase. In support of our model, cells clamped at −80 mV and challenged with a reduced osmotic potential swelled approximately twice as much as cells at +10 mV. The positive RMP may be a protective adaptation that allows chondrocytes to respond to the dramatic osmotic changes, with minimal changes in cell volume. J. Cell. Physiol. 226: 2979–2986, 2011. © 2011 Wiley-Liss, Inc.
publisher	Wiley Subscription Services, Inc., A Wiley Company
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229839/
_version_	1611491632371204096

The Role of the Membrane Potential in Chondrocyte Volume Regulation

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