Open channel block and open channel destabilization: contrasting effects of phenol, TEA(+) and local anaesthetics on Kv1.1 K+ channels

:1(0)(1) Voltage-gated K+ channels are inhibited by a variety of clinical a nd experimental drugs. (2) Complex changes in channel gating suggest mechan isms in which drug affinity depends on channel state. (3) Here, we use the effects of external TEA(+), two local anaesthetics (lidocaine and bupivacai ne), and phenol on rat brain Kvl.l K+ channels expressed in Xenopus oocytes to illustrate three mechanisms. (4) The open state has the highest affinit y in the local anaesthetic model but the lowest in the phenol model, and wh ile local anaesthetics simply block the open channel, phenol can produce a conducting but destabilized open state. (5) All states have equal affinity for external TEA(+). (C) 1998 Elsevier Science Ireland Ltd. All rights rese rved.