Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Poster Abstracts

52-POS Board 52 Voltage-dependent Gating and K + Block in Thetwik-1 K2P Channel.

Ehsan Nematian-Ardestani 1 , Marcus Schewe 2 , Thomas Baukrowitz 2 , Stephen J. Tucker 1 . 1 University of Oxford, Oxford, United Kingdom, 2 University of Kiel, Kiel, Germany. Recently we have shown that nearly all K2P channels can be activated by voltage (Schewe et al, 2016 Cell 164:937-49). In that study, we also demonstrated that this voltage-dependent gating is due to a ‘flux-gating’ mechanism located within the selectivity filter. However, the TWIK-1 channel appeared to be an exception to this general rule because it behaves primarily like a leak channel. Here we now show that TWIK-1 can also exhibit voltage-dependent activation within the physiological voltage range, but only with non-physiological permeant ions such as Rb + and NH4 + . Furthermore, we show that voltage-dependent activation with K + as the permeant ion can also occur, but only at voltages beyond the physiological range. The low functional activity of TWIK-1 appears to result from a combination of different possible mechanisms including post- translational modification, rapid internalization and the existence of a hydrophobic barrier deep within the inner pore. Our results now propose an additional mechanism, namely a strong interaction of K + ions with the selectivity filter, that results in a block at physiological concentrations (IC 50 ~ 2.8 mM). This mechanism explains the unusual voltage-dependent activation of TWIK-1 due to a strong inhibition by K + ions within the filter. These results suggest that, like other K2P channels, TWIK-1 also possesses a voltage-dependent gate within the selectivity filter; however, this mechanism appears exquisitely sensitive to the nature of the permeant ion.

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