Non-linear leak currents affect mammalian neuron physiology

In their seminal works on squid giant axons, Hodgkin and Huxley approximated the membrane leak current as Ohmic, i.e. linear, since in their preparation, sub-threshold current rectification due to the influence of ionic concentration is negligible. Most studies on mammalian neurons have made the sam...

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Main Authors: Shiwei eHuang, Sungho eHong, Erik eDe Schutter
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-11-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00432/full
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author Shiwei eHuang
Shiwei eHuang
Sungho eHong
Erik eDe Schutter
author_facet Shiwei eHuang
Shiwei eHuang
Sungho eHong
Erik eDe Schutter
author_sort Shiwei eHuang
collection DOAJ
description In their seminal works on squid giant axons, Hodgkin and Huxley approximated the membrane leak current as Ohmic, i.e. linear, since in their preparation, sub-threshold current rectification due to the influence of ionic concentration is negligible. Most studies on mammalian neurons have made the same, largely untested, assumption. Here we show that the membrane time constant and input resistance of mammalian neurons (when other major voltage-sensitive and ligand-gated ionic currents are discounted) varies non-linearly with membrane voltage, following the prediction of a Goldman-Hodgkin-Katz-based passive membrane model. The model predicts that under such conditions, the time constant/input resistance-voltage relationship will linearize if the concentration differences across the cell membrane are reduced. These properties were observed in patch-clamp recordings of cerebellar Purkinje neurons (in the presence of pharmacological blockers of other background ionic currents) and were more prominent in the sub-threshold region of the membrane potential. Model simulations showed that the non-linear leak affects voltage-clamp recordings and reduces temporal summation of excitatory synaptic input. Together, our results demonstrate the importance of trans-membrane ionic concentration in defining the functional properties of the passive membrane in mammalian neurons as well as other excitable cells.
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spelling doaj.art-1968a0fb2ba4472ba767cffe91d6eb582022-12-21T22:08:13ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022015-11-01910.3389/fncel.2015.00432160172Non-linear leak currents affect mammalian neuron physiologyShiwei eHuang0Shiwei eHuang1Sungho eHong2Erik eDe Schutter3Okinawa Institute of Science and Technology Graduate UniversityAustralian National UniversityOkinawa Institute of Science and Technology Graduate UniversityOkinawa Institute of Science and Technology Graduate UniversityIn their seminal works on squid giant axons, Hodgkin and Huxley approximated the membrane leak current as Ohmic, i.e. linear, since in their preparation, sub-threshold current rectification due to the influence of ionic concentration is negligible. Most studies on mammalian neurons have made the same, largely untested, assumption. Here we show that the membrane time constant and input resistance of mammalian neurons (when other major voltage-sensitive and ligand-gated ionic currents are discounted) varies non-linearly with membrane voltage, following the prediction of a Goldman-Hodgkin-Katz-based passive membrane model. The model predicts that under such conditions, the time constant/input resistance-voltage relationship will linearize if the concentration differences across the cell membrane are reduced. These properties were observed in patch-clamp recordings of cerebellar Purkinje neurons (in the presence of pharmacological blockers of other background ionic currents) and were more prominent in the sub-threshold region of the membrane potential. Model simulations showed that the non-linear leak affects voltage-clamp recordings and reduces temporal summation of excitatory synaptic input. Together, our results demonstrate the importance of trans-membrane ionic concentration in defining the functional properties of the passive membrane in mammalian neurons as well as other excitable cells.http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00432/fullPassive membrane propertiesionic concentration-dependenceGoldman-Hodgkin-Katz equationtime constant and input resistancecerebellar Purkinje neurons.
spellingShingle Shiwei eHuang
Shiwei eHuang
Sungho eHong
Erik eDe Schutter
Non-linear leak currents affect mammalian neuron physiology
Frontiers in Cellular Neuroscience
Passive membrane properties
ionic concentration-dependence
Goldman-Hodgkin-Katz equation
time constant and input resistance
cerebellar Purkinje neurons.
title Non-linear leak currents affect mammalian neuron physiology
title_full Non-linear leak currents affect mammalian neuron physiology
title_fullStr Non-linear leak currents affect mammalian neuron physiology
title_full_unstemmed Non-linear leak currents affect mammalian neuron physiology
title_short Non-linear leak currents affect mammalian neuron physiology
title_sort non linear leak currents affect mammalian neuron physiology
topic Passive membrane properties
ionic concentration-dependence
Goldman-Hodgkin-Katz equation
time constant and input resistance
cerebellar Purkinje neurons.
url http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00432/full
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AT shiweiehuang nonlinearleakcurrentsaffectmammalianneuronphysiology
AT sunghoehong nonlinearleakcurrentsaffectmammalianneuronphysiology
AT erikedeschutter nonlinearleakcurrentsaffectmammalianneuronphysiology