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. 1990 May;424:387–409. doi: 10.1113/jphysiol.1990.sp018073

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

M R Duchen 1
PMCID: PMC1189819  PMID: 2391654

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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Selected References

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