title: Chloride conductance and extracellular potassium concentration interact to modify the excitability of rat optic nerve fibres.
abstract: The excitability of developing rat optic nerves has been studied under conditions in which extracellular Cl- was replaced with other anions. In nerves younger than 3 days old, replacing Cl- with propionate or SO4(2-) usually led to spontaneous and repetitive cycling of extracellular K+ concentration ([K+]o). [K+]o reached peaks of 8-12 mM and then fell transiently below the base-line level of 5 mM before increasing again. This cycling behaviour continued, with a wave-length of 1-2 min, for as long as 2 h. Nerves older than 5 days either did not cycle or did so only transiently. Substitution of ten different anions for Cl- indicated that a minimum hydrated radius, between that of BrO3- and HCO3-, was necessary to induce cycling behaviour. Cycling behaviour was abolished by the Na+-channel blocker tetrodotoxin. Reduction of the bath [K+] to 2.5 mM slowed the frequency of spontaneous cycles; a bath [K+] of 1 mM abolished them. When the temperature was lowered, cycle frequency slowed. Substitution of large anions for Cl- enhanced axonal excitability. This was inferred from the prevalence of spontaneous action potentials during cycling behaviour, and from the generation of relatively large evoked increases of [K+]o. Cycling behaviour is hypothesized to result from a repetition of the following three processes: (i) spontaneous axonal firing elicits a gradual increase in [K+]o which increases axonal excitability and facilitates further K+ release, (ii) axonal firing and K+ release are eventually halted by a combination of depolarization block, intracellular Na+ accumulation and hyperpolarization from electrogenic pumping, (iii) recovery of [K+]o to its minimal value depends on active K+ reuptake mediated by a highly stimulated axonal Na+-K+-ATPase. We conclude that a large proportion of the resting membrane conductance of optic nerve fibres is Cl- specific. A high Cl- conductance may stabilize fine central axons against the depolarizing effects of [K+]o increases.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000375:Aging; D000818:Animals; D000838:Anions / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism; D009900:Optic Nerve / Q000378:metabolism / Q000502:physiology*; D010507:Periodicity; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000838:Anions; D002712:Chlorides; D007473:Ion Channels; D013779:Tetrodotoxin; D012964:Sodium; D011188:Potassium