Abstract:
:Two-pore domain (K2P) K(+) channels are major regulators of excitability that endow cells with an outwardly rectifying background "leak" conductance. In some K2P channels, strong voltage-dependent activation has been observed, but the mechanism remains unresolved because they lack a canonical voltage-sensing domain. Here, we show voltage-dependent gating is common to most K2P channels and that this voltage sensitivity originates from the movement of three to four ions into the high electric field of an inactive selectivity filter. Overall, this ion-flux gating mechanism generates a one-way "check valve" within the filter because outward movement of K(+) induces filter opening, whereas inward movement promotes inactivation. Furthermore, many physiological stimuli switch off this flux gating mode to convert K2P channels into a leak conductance. These findings provide insight into the functional plasticity of a K(+)-selective filter and also refine our understanding of K2P channels and the mechanisms by which ion channels can sense voltage.
journal_name
Celljournal_title
Cellauthors
Schewe M,Nematian-Ardestani E,Sun H,Musinszki M,Cordeiro S,Bucci G,de Groot BL,Tucker SJ,Rapedius M,Baukrowitz Tdoi
10.1016/j.cell.2016.02.002subject
Has Abstractpub_date
2016-02-25 00:00:00pages
937-49issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(16)30068-Xjournal_volume
164pub_type
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