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.
Kaspar
A
A
Abteilung für Allgemeine Physiologie der Universität Ulm, Germany.
Brinkmeier
H
H
Rüdel
R
R
D000779:Anesthetics, Local / Q000494:pharmacology*; D002478:Cells, Cultured; D004594:Electrophysiology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism; D015290:Second Messenger Systems; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin