The Resting Potential and K+ Currents in Primary Human Articular Chondrocytes
Human transplant programs provide significant opportunities for detailed in vitro assessments of physiological properties of selected tissues and cell types. We present a semi-quantitative study of the fundamental electrophysiological/biophysical characteristics of human chondrocytes, focused on K+...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2018-09-01
|
Series: | Frontiers in Physiology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2018.00974/full |
id |
doaj-ebe40a63390e46a989f4902cc2b66bbf |
---|---|
record_format |
Article |
spelling |
doaj-ebe40a63390e46a989f4902cc2b66bbf2020-11-24T23:58:12ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-09-01910.3389/fphys.2018.00974384864The Resting Potential and K+ Currents in Primary Human Articular ChondrocytesMary M. Maleckar0Mary M. Maleckar1Robert B. Clark2Bartholomew Votta3Wayne R. Giles4Simula Research Laboratory, Center for Biomedical Computing and Center for Cardiological Innovation, Oslo, NorwayAllen Institute for Cell Science, Seattle, WA, United StatesFaculty of Kinesiology, University of Calgary, Calgary, AB, CanadaGlaxo Smith Kline, Collegeville, PA, United StatesFaculties of Kinesiology and Medicine, University of Calgary, Calgary, AB, CanadaHuman transplant programs provide significant opportunities for detailed in vitro assessments of physiological properties of selected tissues and cell types. We present a semi-quantitative study of the fundamental electrophysiological/biophysical characteristics of human chondrocytes, focused on K+ transport mechanisms, and their ability to regulate to the resting membrane potential, Em. Patch clamp studies on these enzymatically isolated human chondrocytes reveal consistent expression of at least three functionally distinct K+ currents, as well as transient receptor potential (TRP) currents. The small size of these cells and their exceptionally low current densities present significant technical challenges for electrophysiological recordings. These limitations have been addressed by parallel development of a mathematical model of these K+ and TRP channel ion transfer mechanisms in an attempt to reveal their contributions to Em. In combination, these experimental results and simulations yield new insights into: (i) the ionic basis for Em and its expected range of values; (ii) modulation of Em by the unique articular joint extracellular milieu; (iii) some aspects of TRP channel mediated depolarization-secretion coupling; (iv) some of the essential biophysical principles that regulate K+ channel function in “chondrons.” The chondron denotes the chondrocyte and its immediate extracellular compartment. The presence of discrete localized surface charges and associated zeta potentials at the chondrocyte surface are regulated by cell metabolism and can modulate interactions of chondrocytes with the extracellular matrix. Semi-quantitative analysis of these factors in chondrocyte/chondron function may yield insights into progressive osteoarthritis.https://www.frontiersin.org/article/10.3389/fphys.2018.00974/fullhuman chondrocytepatch clamp recordingsK+ currentsTRP channelsmathematical modelresting membrane potential |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mary M. Maleckar Mary M. Maleckar Robert B. Clark Bartholomew Votta Wayne R. Giles |
spellingShingle |
Mary M. Maleckar Mary M. Maleckar Robert B. Clark Bartholomew Votta Wayne R. Giles The Resting Potential and K+ Currents in Primary Human Articular Chondrocytes Frontiers in Physiology human chondrocyte patch clamp recordings K+ currents TRP channels mathematical model resting membrane potential |
author_facet |
Mary M. Maleckar Mary M. Maleckar Robert B. Clark Bartholomew Votta Wayne R. Giles |
author_sort |
Mary M. Maleckar |
title |
The Resting Potential and K+ Currents in Primary Human Articular Chondrocytes |
title_short |
The Resting Potential and K+ Currents in Primary Human Articular Chondrocytes |
title_full |
The Resting Potential and K+ Currents in Primary Human Articular Chondrocytes |
title_fullStr |
The Resting Potential and K+ Currents in Primary Human Articular Chondrocytes |
title_full_unstemmed |
The Resting Potential and K+ Currents in Primary Human Articular Chondrocytes |
title_sort |
resting potential and k+ currents in primary human articular chondrocytes |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2018-09-01 |
description |
Human transplant programs provide significant opportunities for detailed in vitro assessments of physiological properties of selected tissues and cell types. We present a semi-quantitative study of the fundamental electrophysiological/biophysical characteristics of human chondrocytes, focused on K+ transport mechanisms, and their ability to regulate to the resting membrane potential, Em. Patch clamp studies on these enzymatically isolated human chondrocytes reveal consistent expression of at least three functionally distinct K+ currents, as well as transient receptor potential (TRP) currents. The small size of these cells and their exceptionally low current densities present significant technical challenges for electrophysiological recordings. These limitations have been addressed by parallel development of a mathematical model of these K+ and TRP channel ion transfer mechanisms in an attempt to reveal their contributions to Em. In combination, these experimental results and simulations yield new insights into: (i) the ionic basis for Em and its expected range of values; (ii) modulation of Em by the unique articular joint extracellular milieu; (iii) some aspects of TRP channel mediated depolarization-secretion coupling; (iv) some of the essential biophysical principles that regulate K+ channel function in “chondrons.” The chondron denotes the chondrocyte and its immediate extracellular compartment. The presence of discrete localized surface charges and associated zeta potentials at the chondrocyte surface are regulated by cell metabolism and can modulate interactions of chondrocytes with the extracellular matrix. Semi-quantitative analysis of these factors in chondrocyte/chondron function may yield insights into progressive osteoarthritis. |
topic |
human chondrocyte patch clamp recordings K+ currents TRP channels mathematical model resting membrane potential |
url |
https://www.frontiersin.org/article/10.3389/fphys.2018.00974/full |
work_keys_str_mv |
AT marymmaleckar therestingpotentialandkcurrentsinprimaryhumanarticularchondrocytes AT marymmaleckar therestingpotentialandkcurrentsinprimaryhumanarticularchondrocytes AT robertbclark therestingpotentialandkcurrentsinprimaryhumanarticularchondrocytes AT bartholomewvotta therestingpotentialandkcurrentsinprimaryhumanarticularchondrocytes AT waynergiles therestingpotentialandkcurrentsinprimaryhumanarticularchondrocytes AT marymmaleckar restingpotentialandkcurrentsinprimaryhumanarticularchondrocytes AT marymmaleckar restingpotentialandkcurrentsinprimaryhumanarticularchondrocytes AT robertbclark restingpotentialandkcurrentsinprimaryhumanarticularchondrocytes AT bartholomewvotta restingpotentialandkcurrentsinprimaryhumanarticularchondrocytes AT waynergiles restingpotentialandkcurrentsinprimaryhumanarticularchondrocytes |
_version_ |
1725451203414851584 |