Editors' ChoiceStructural Biology

A sensitive regulator of cellular potassium

Sci. Signal.  17 Mar 2015:
Vol. 8, Issue 368, pp. ec63
DOI: 10.1126/scisignal.aab1181

A class of potassium channels called K2P channels modulates resting membrane potential in most cells. The channels are regulated by multiple ligands, including the antidepressant drug Prozac, as well as factors such as mechanical stretch and voltage. Dong et al. determined the structure of the human K2P channel, TREK-2, in two conformations and bound to a metabolite of Prozac. The structures show how ligand binding or mechanical stretch might induce switching between the states. Although both states have open channels, one appears primed for gating. A Prozac metabolite binds to the primed state and prevents conformational switching. K2P channels are not an intended target of Prozac, but their inhibition may contribute to side effects.

Y. Y. Dong, A. C. W. Pike, A. Mackenzie, C. McClenaghan, P. Aryal, L. Dong, A. Quigley, M. Grieben, S. Goubin, S. Mukhopadhyay, G. F. Ruda, M. V. Clausen, L. Cao, P. E. Brennan, N. A. Burgess-Brown, M. S. P. Sansom, S. J. Tucker, E. P. Carpenter, K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac. Science 347, 1256–1259 (2015). [Abstract] [Full Text]