Voltage-dependent gating at the KcsA selectivity filter

Julio F Cordero-Morales¹, Luis G Cuello^1, 2 & Eduardo Perozo^1, 2

¹  Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22906, USA.

²  Present address: Institute of Molecular Pediatrics Science and Department of Biochemistry and Molecular Biology, University of Chicago, Pritzker School of Medicine, 929 E 57^th Street, W206 Chicago, Illinois 60637, USA.

The prokaryotic K⁺ channel KcsA, although lacking a 'standard' voltage-sensing domain, shows voltage-dependent gating that leads to an increase in steady-state open probability of almost two orders of magnitude between +150 and -150 mV. Here we show that voltage-dependent gating in KcsA is associated with the movement of 0.7 equivalent electronic charges. This charge movement produces an increase in the rate of entry into a long-lived inactivated state and seems to be independent of the proton-activation mechanism. Charge neutralization at position 71 renders the channel essentially voltage-independent by preventing entry into the inactivated state. A mechanism for voltage-dependent gating at the selectivity filter is proposed that is based on the reorientation of the carboxylic moiety of Glu71 and its influence in the conformational dynamics of the selectivity filter.

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