title: Excitatory actions of GABA mediate severe-hypoxia-induced depression of neuronal activity in the pond snail (Lymnaea stagnalis).
abstract: To characterize the effect of severe hypoxia on neuronal activity, long-term intracellular recordings were made from neurones in the isolated central ring ganglia of Lymnaea stagnalis. When a neurone at rest in normoxia was subjected to severe hypoxia, action potential firing frequency decreased by 38% (from 2.4-1.5 spikes s(-1)), and the resting membrane potential hyperpolarized from -70.3 to -75.1 mV. Blocking GABA(A) receptor-mediated synaptic transmission with the antagonist bicuculline methiodide (100 micromol l(-1)) decreased neuronal activity by 36%, and prevented any further changes in response to severe hypoxia, indicating that GABAergic neurotransmission mediates the severe hypoxia-induced decrease in neuronal activity. Puffing 100 micromol l(-1) GABA onto the cell body produced an excitatory response characterized by a transient increase in action potential (AP) firing, which was significantly decreased in severe hypoxia. Perturbing intracellular chloride concentrations with the Na+/K+/Cl- (NKCC1) cotransporter antagonist bumetanide (100 micromol l(-1)) decreased AP firing by 40%, consistent with GABA being an excitatory neurotransmitter in the adult Lymnaea CNS. Taken together, these studies indicate that severe hypoxia reduces the activity of NKCC1, leading to a reduction in excitatory GABAergic transmission, which results in a hyperpolarization of the resting membrane potential (Vm) and as a result decreased AP frequency.
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, Ontario, Canada.
authors.forename: Una
authors.initials: U
authors.lastname: Cheung
authors.forename: Mehrnoush
authors.initials: M
authors.lastname: Moghaddasi
authors.forename: Hannah L
authors.initials: HL
authors.lastname: Hall
authors.forename: J J B
authors.initials: JJ
authors.lastname: Smith
authors.forename: Leslie T
authors.initials: LT
authors.lastname: Buck
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Woodin
mesh_terms: D000200:Action Potentials; D000818:Animals; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000502:physiology*; D066298:In Vitro Techniques; D008195:Lymnaea / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010100:Oxygen; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D005680:gamma-Aminobutyric Acid; D010100:Oxygen