Local anaesthetic-like effect of interleukin-2 on muscular Na+ channels: no evidence for involvement of the IL-2 receptor.

The effects of interleukin-2 (IL-2) on muscular Na+ currents were studied in human myoballs. The transient Na+ inward currents, elicited by repetitive depolarizations at 1 Hz and recorded in the whole-cell mode, were inhibited by the cytokine, the half-maximum effect occurring at about 500 U/ml. The effects resembled those of local anaesthetics without use dependence, as the inactivation (h infinity) curve was shifted in a negative direction while the current/voltage curve was not affected. As with these local anaesthetics, depolarization at 1, 4 and 8 Hz in the presence of IL-2 did not produce any cumulative block. The interaction of IL-2 with the Na+ channels is very fast (within ms) and it is suggested that it occurs when the Na+ channels are in the state of fast inactivation. The recovery from inactivation was only slightly slowed by IL-2, in agreement with the absence of any use dependence. All effects were readily reversible on washout of the cytokine. The effects were seen both in tetrodotoxin-(TTX)-sensitive adult Na+ channels and in TTX-insensitive juvenile channels. In contrast to the whole-cell configuration, no inhibition was visible in the attached-patch configuration. Further, the preincubation with an anti-IL-2-receptor antibody did not prevent the inhibitory effect of IL-2 on the Na+ currents. It is concluded that the cytokine blocks the voltage-dependent muscular Na+ channels by keeping the channels in the state of fast inactivation. An IL-2 receptor and a second messenger system are not likely to be involved in this reaction.