Analysis of a decreased Na+ conductance by tumor necrosis factor in identified neurons of Aplysia kurodai.
The ionic mechanisms of the effect of extracellularly ejected recombinant human tumor necrosis factor-alpha (rhTNF-alpha) on the membrane of identified neurons R9 and R10 of Aplysia kurodai was investigated with conventional voltage-clamp, micropressure ejection, and ion substitution techniques. Micropressure-ejected rhTNF caused a marked hyperpolarization in the unclamped neuron. Clamping the same neuron at it resting potential level (-60 mV) and reejecting rhTNF-alpha with the same dose produced a slow outward current [Io (TNF)] associated with a decrease in input membrane conductance. Io (TNF) was decreased by depolarization and increased by hyperpolarization. The extrapolated reversal potential of Io (TNF) was approximately +10 mV. Ion substitution and pharmacological experiments suggest that Io (TNF) in identified neurons R9 and R10 of A. kurodai is due to a decreased Na+ conductance but not due to an activation of the Na(+)-K+ pump. Our results demonstrate that the immunomodulator TNF can act directly on the nervous system as well as on the immune system.
Sawada
M
M
Department of Physiology, Shimane Medical University, Izumo, Japan.
Hara
N
N
Maeno
T
T
D000818:Animals; D001048:Aplysia / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002712:Chlorides / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D002712:Chlorides; D011994:Recombinant Proteins; D015222:Sodium Channels; D013757:Tetraethylammonium Compounds; D014409:Tumor Necrosis Factor-alpha; D013779:Tetrodotoxin; D010042:Ouabain; D011188:Potassium; D002118:Calcium