Properties of the resting membrane potential in central myelinated axons during normoxic conditions and metabolic inhibition.

dc.contributor.advisorStys, P. K.,
dc.contributor.authorLeppanen, Lisa Livia.
dc.identifier.citationSource: Masters Abstracts International, Volume: 36-01, page: 0126.
dc.description.abstractCompound resting membrane potential was studied in the rat optic nerve, a representative model of myelinated CNS axons, using the grease gap recording technique which measures a reliable fraction of the true intra-axonal potential. Studies were performed during (1) normoxic conditions, (2) glycolytic inhibition, or (3) chemical anoxia at 37$\sp\circ$C, in order to characterize ions and channels promoting membrane depolarization. Ouabain, an antagonist of Na$\sp+$,K$\sp+$-ATPase, caused strong depolarization, showing that membrane potential is critically dependent on Na$\sp+$,K$\sp+$-ATPase. In addition, inhibiting energy metabolism during ouabain exposure produced further depolarization, suggesting additional ATP-dependent, ouabain-insensitive ion transport systems. Glycolysis was blocked with iodoacetate or deoxyglucose, evoking a response consisting of four distinct phases. An initial transient hyperpolarization (phase 1) preceded a rapid depolarizing response (phase 2). Phase 2 was interrupted by a second brief hyperpolarization (phase 3) which was followed by a gradual depolarization (phase 3). Chemical anoxia (cyanide) immediately depolarized the nerve, with only a small inflection introducing a final slow depolarizing response. Addition of ouabain to cyanide-treated nerves caused an additional depolarization indicating a minor glycolytic contribution to Na$\sp+$,K$\sp+$-ATPase, which seems preferentially fueled by mitochondrial ATP in optic nerve. Hyperpolarizing phases 1 and 3 induced by iodoacetate exposure and the inflection during cyanide treatment were abolished by zero-Ca$\sp{2+}$/EGTA treatment. Block of Na$\sp+$ channels with tetrodotoxin, the local anesthetics, procaine or QX-314, or replacement of Na$\sp+$ with the impermeant cation choline significantly reduced depolarization during iodoacetate or cyanide application, indicating that axonal membrane depolarization requires Na$\sp+$ influx which secondarily allows electroneutral K$\sp+$ efflux and depolarization. (Abstract shortened by UMI.)
dc.format.extent113 p.
dc.publisherUniversity of Ottawa (Canada)
dc.subject.classificationBiology, Neuroscience.
dc.titleProperties of the resting membrane potential in central myelinated axons during normoxic conditions and metabolic inhibition.
CollectionTh├Ęses, 1910 - 2010 // Theses, 1910 - 2010

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