Ammonia and disinhibition in cat motor cortex by ammonium acetate, monofluoroacetate and insulin-induced hypoglycemia.
Ammonia intoxication abolished the suppression of action potential generation by cortical postsynaptic inhibition due to the inactivation of neuronal Cl- extrusion. The disinhibition by ammonia intoxication occurred when ammonia concentrations in the cerebral cortex were increased to 320% of normal. Fluoroacetate poisoning and insulin-induced hypoglycemia, which are known to increase ammonia concentrations in the CNS and previously have been shown to inactivate Cl- extrusion in spinal motoneurons, abolished the suppression of action potential generation by cortical postsynaptic inhibition like ammonia intoxication. This disinhibition occurred at unchanged cerebral ammonia concentrations. The effect of fluoroacetate and insulin induced hypoglycemia on cortical postsynaptic inhibition is either due to a direct, i.e. not ammonia mediated, inactivation of neuronal Cl- extrusion or due to a disturbance of the synaptic mechanisms mediated by the transmitter of cortical inhibition, GABA. Toxic-metabolic encephalopathies which increase cerebral ammonia concentrations beyond 320% of normal may produce a dysfunction of the CNS due to inactivation of neuronal Cl- extrusion leading to ineffective cortical inhibition. However, in fluoroacetate poisoning and insulin-induced hypoglycemia increased ammonia concentrations in the CNS have only a secondary role in initiating a dysfunction of the CNS since disinhibition occurs before ammonia concentrations increase.
D000085:Acetates; D000200:Action Potentials / Q000187:drug effects; D000641:Ammonia / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D005463:Fluoroacetates / Q000494:pharmacology*; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology*; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*
D000085:Acetates; D005463:Fluoroacetates; D007328:Insulin; D000644:Quaternary Ammonium Compounds; D000641:Ammonia; C014815:fluoroacetic acid; C018824:ammonium acetate