Mechanisms of hyperpolarization induced by two cytokines, hTNFα and hIL-1α in neurons of the mollusc, Onchidium

Abstract

The voltage and current responses induced by extracellular tumor necrosis factor (hTNFα) or interleukin-1 (hIL-1α) on the Be-1 and Es-1 neurons of the Onchidium ganglia were examined. Pressure-ejected hTNFα or hIL-1α produced an inhibitory, hyperpolarized effect in unclamped neurons. In the same neurons voltage-clamped at their resting potential levels, the same hTNFα or hIL-1α elicited an outward current having a time course similar to that of the hyperpolarization, associated with a decreased membrane conductance. The hTNFα- or hIL-1α-induced outward current did not reverse even at positive membrane potentials considerably above +100 mV in the absence of ouabain (a specific blocker of Na-pump). In the presence of ouabain, the hTNFα- or hIL-1α-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 Ca 2+, however, significantly altered the current induced by hTNFα or hIL-1α. These suggest that the hTNFα- or hIL-1α-induced hyperpolarization or outward current response is mediated by two mechanisms, a decrease in Na + conductance and activation of the Na-pump.