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Cited by 121Ion channel regulation and functionMitochondrial Function and PathologyIon Channels and Receptors

Effects of metabolic inhibition on the membrane properties of isolated mouse primary sensory neurones

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Duchen, M R·1990·The Journal of Physiology
DOI 10.1113/jphysiol.1990.sp018073PMC PMC1189819
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Abstract

1. The patch-clamp technique has been used to investigate the mechanisms that couple membrane excitability to metabolism in neurones isolated from mouse dorsal root ganglia. 2. Blockade of electron transport by cyanide (CN-), reduction of the mitochondrial membrane potential with carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (FCCP), removal of glucose or inhibition of glycolysis with idoacetic acid (IAA), all increased a K+ conductance (gK), which could be sufficient to shunt action potentials. 3. The K+ conductance was reduced by incubation of cells in Ca2(+)-free solutions or by increasing the Ca2+ buffering power of pipette-filling solutions. The Ca2+ ionophore, ionomycin, also increased a K+ conductance, and current fluctuation analysis showed that the channels carrying the current induced by both ionomycin and by CN- had a similar mean conductance of circa 9 pS. Thus, increased gK was a Ca2(+)-dependent K+ conductance, gK(Ca), reflecting a rise in resting [Ca2+]i. 4. The conductance was not affected by inclusion of ATP or an ATP-regenerating system in the pipette, suggesting that the underlying rise in [Ca2+] is not due directly to loss of ATP, and confirming that the increased gK is not carried through ATP-dependent K+ channels. 5. Voltage-gated K+ currents evoked by membrane depolarization were increased by CN- or glucose removal. The current-voltage relation of the increased gK mirrored the voltage dependence of Ca2+ entry, and thus reflects impaired cellular handling of the Ca2+ load imposed by depolarization. 6. The rise in [Ca2+]i and altered Ca2+ buffering capacity induced by metabolic blockade affected several other conductances: (i) a Ca2(+)-dependent chloride current was increased. (ii) Both the low-threshold transient and high-threshold sustained voltage-gated Ca2+ currents were attenuated and their thresholds were shifted in the hyperpolarizing direction. (iii) The inward current activated by hyperpolarization. IH, seen in large cells, was attenuated by either metabolic blockade or ionomycin. 7. The responses of these neurones to impaired metabolism thus depend largely on the effects of raised [Ca2+]i on the populations of channels expressed by the cells. These changes in membrane properties could account for some of the changes in neuronal behaviour seen during the clinical states of hypoxia or hypoglycaemia, underlying changes in central nervous system function.

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Authors
Duchen, M. R.
Affiliations
University College London (GB)
Corresponding author
Duchen, M R
ORCID
Duchen, M R
Venue
The Journal of Physiology
Publisher
Wiley
Published
1990-05
Volume
424
Issue
1
Pages
387-409
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1113/jphysiol.1990.sp018073
PMC
PMC1189819
OpenAlex
W2020061801
Cited by
121
References
53
Citations by year
2025: 1 · 2023: 1 · 2021: 1 · 2019: 2 · 2018: 1 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 4 · 2012: 3
FWCI
3.14
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords
metabolic inhibition, dorsal root ganglion neurons, primary sensory neurons, membrane excitability, intracellular calcium, calcium-dependent potassium conductance, voltage-gated calcium currents, inward rectifier potassium current, calcium buffering, cyanide, FCCP, ionomycin, hypoxia, hypoglycemia, ATP depletion, shunting
MeSH terms
Adenosine Triphosphate, Animals, Calcium, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone, Cell Compartmentation, Electron Transport, Ganglia, Spinal, Glycolysis, Intracellular Membranes, Iodoacetates, Membrane Potentials, Mitochondria, Neurons, Sodium Cyanide, Potassium Channels, Ion Channel Gating, Ionomycin, Iodoacetic Acid, Mice

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