Mechanisms of hyperpolarization induced by two cytokines, hTNF alpha and hIL-1 alpha in neurons of the mollusc, Onchidium.
The voltage and current responses induced by extracellular tumor necrosis factor (hTNF alpha) or interleukin-1 (hIL-1 alpha) on the Be-1 and Es-1 neurons of the Onchidium ganglia were examined. Pressure-ejected hTNF alpha or hIL-1 alpha produced an inhibitory, hyperpolarized effect in unclamped neurons. In the same neurons voltage-clamped at their resting potential levels, the same hTNF alpha or hIL-1 alpha elicited an outward current having a time course similar to that of the hyperpolarization, associated with a decreased membrane conductance. The hTNF alpha- or hIL-1 alpha-induced outward current did not reverse even at positive membrane potentials considerably above + 100 mV in the absence ouabain (a specific blocker of Na-pump). In the presence of ouabain, the hTNF alpha- or hIL-1 alpha-induced current was reduced over a wide range of membrane potential, so that the current reversed at about + 20 mV. Lowering the external Na+ concentration from 450 to 200 mM in the presence of ouabain, shifted the reversal potential from + 20 to 0 mV, to near the shift value of 20.8 mV predicted by the Nernst equation for a Na(+)-selective conductance. Neither an increase nor a decrease of extracellular K+, Cl- or Ca2+, however, significantly altered the current induced by hTNF alpha or hIL-1 alpha. These suggest that the hTNF alpha- or hIL-1 alpha-induced hyperpolarization or outward current response is mediated by two mechanisms, a decrease in Na+ conductance and activation of the Na-pump.
Mimura
Y
Y
Third Department of Internal Medicine, School of Medicine, Kagoshima University, Japan.
Gotow
T
T
Nishi
T
T
Osame
M
M
D000818:Animals; D016207:Cytokines / Q000494:pharmacology*; D004594:Electrophysiology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007477:Ions; D008974:Mollusca; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016207:Cytokines; D007375:Interleukin-1; D007477:Ions; D014409:Tumor Necrosis Factor-alpha; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase