Comment on the paper by Lee et al. from A.M.Kariev and M.E. Green

The paper by Lee et al shows how the gate of the Kv1.2 channel can be closed by protonation of two key amino acids. We have earlier suggested that gating of Kv1.2 and related channels was a consequence of the motion of protons rather than the S4 segment. This is supported by the existence of the Hv1 channel [1, 2], the extracellular section of which strongly resembles the extracellular section of the voltage sensing domain of Kv1.2; this means that the extracellular section of the Kv1.2 must also be able to conduct protons; we have carried out quantum calculations that show in detail what a first step in a proton cascade would be, under a change in electric field of approximately the same magnitude as in a voltage sensing domain [3]. We have also reviewed the overall evidence concerning gating in these channels, [4-6] and suggested that the evidence can be interpreted without invoking S4 motion, with H+ motion providing the gating current. We find the Lee, et al conclusion entirely reasonable, and suggest that it can be carried further; the gating current can be accounted for by proton motion, and a proton cascade starting at the extracellular end of the voltage sensing domain extends to the two amino acids whose protonation Lee et al find closes the gate

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