Electrical properties of oligodendrocyte lineage cells.
Doctoral thesis, UCL (University College London).
Oligodendrocytes wrap myelin around axons in the central nervous system and thus speed the propagation of action potentials along the axons, but in pathological conditions oligodendrocytes become damaged, causing mental and physical disability. In this thesis I investigated the membrane properties of oligodendrocyte lineage cells in the corpus callosum, cerebellum and optic nerve. Oligodendrocyte precursor cells (OPCs) in the corpus callosum and cerebellar white matter fell into two classes, expressing and lacking voltage-gated Na+ channels. The cells with Na+ channels also showed more outward current at positive potentials, probably mediated by voltage-gated K+ channels. Immature and mature oligodendrocyte membrane currents were essentially time-independent. Correlating the dye-fill morphology and electrical properties of mature oligodendrocytes showed the specific membrane conductance of oligodendrocytes to differ 2- to 4-fold between oligodendrocytes in the corpus callosum and cerebellum. Ischaemia abolished the compound action potential of the optic nerve and corpus callosum, and generated a rise of extracellular glutamate concentration that evoked an inward membrane current in corpus callosum oligodendrocytes. Blocking NMDA receptors with memantine or MK-801 partly protected the compound action potential against the deleterious effects of ischaemia, suggesting that activation of oligodendrocyte NMDA receptors is partly responsible for the loss of action potential propagation. An analysis was carried out of the signalling mechanisms contributing to the rundown of oligodendrocyte NMDA responses seen on repeated application of NMDA. These mechanisms differed for corpus callosal and cerebellar oligodendrocytes and, for cerebellar oligodendrocytes, differed from the mechanism producing rundown of neuronal NMDA responses. Some OPCs expressing voltage-gated Na+ channels received glutamatergic and GABAergic synaptic input, and generated action potentials, but these action potentials apparently did not initiate signalling to other cells nearby. I tentatively conclude that action potentials in OPCs may serve a cell intrinsic role, such as regulating myelination.
|Title:||Electrical properties of oligodendrocyte lineage cells|
|Additional information:||Authorisation for digitisation not received|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Neuroscience, Physiology and Pharmacology|
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