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- W1997342014 abstract "Local anaesthetics (LAs) are generally assumed to block action potentials by binding to Nav channels, preferentially when in inactivated and/or open state. Recently, it has been suggested that they, in addition or preferentially, bind to Nav channels when in intermediate closed states. This is based on the finding that LAs reduce the peak current more at low voltage steps than at high in voltage clamp experiments.In previous studies we have concluded that LAs preferentially block Kv channels by binding to exclusively open channels. In the present study we have reanalysed the effect, with special reference to the new findings of closed state binding. We analysed the effects of bupivacaine on Kv3.1 channels expressed in Xenopus oocytes. In contrast to the results from the Na studies, bupivacaine reduced the early current more at higher voltages than at lower. Nevertheless, analysing kinetic models we found that the results are explained by binding preferentially to open channels.We thus conclude that bupivacaine block K channels mainly in the open state. We also conclude that a time and voltage-dependent block, similar to that reported for Na channels, does not necessarily imply binding of channels in different closed states. Furthermore, the results stress the general fact that a block of the early current in voltage clamp experiments does not necessarily imply that LAs bind to the channel when in closed state, contrary to a widely held view." @default.
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- W1997342014 date "2013-01-01" @default.
- W1997342014 modified "2023-10-03" @default.
- W1997342014 title "Local Anesthetics on Kv Channels - Closed State Binding of Bupivacaine?" @default.
- W1997342014 doi "https://doi.org/10.1016/j.bpj.2012.11.726" @default.
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