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Acta Physiologica Congress

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Acta Physiologica 2011; Volume 201, Supplement 682
The 90th Annual Meeting of The German Physiological Society
3/26/2011-3/29/2011
Regensburg, Germany


MODE SHIFT OF THE VOLTAGE SENSORS IN SHAKER K+ CHANNELS IS CAUSED BY ENERGETIC COUPLING TO THE PORE DOMAIN.
Abstract number: P260

*Haddad1 G.A., Blunck1 R.

The voltage sensors (S1-S4) of Kv channels are known to undergo a conformational change when triggered by membrane depolarisation that subsequently leads to opening of the central pore (S5-S6) and ion conduction. The electromechanical coupling between these domains is mediated by two well conserved regions: the C-terminus of the S6 segment and the S4-S5 linker. Upon change in the membrane potential, the structural rearrangements induced by the charged S4 segment can be measured as gating currents. During prolonged depolarization, voltage-gated ion channels present a behaviour called the "mode-shift". This shift essentially affects the energy required by the system to bring all sensors back to their resting state. To understand the structural cause of this process, we investigated the coupling between the pore and voltage sensor and its influence on the mode shift. In our approach we used the cut-open voltage clamp fluorometry method to simultaneously measure gating or ionic currents and conformational changes of the S4 segment. We identified mutations that fully uncouple voltage sensors from the pore domain thus eliminating the mutual influence of these two domains on one another. The results show that, when eliminating the coupling between these domains, the voltage sensors require less energy to move. At the same time the mode shift occurring during prolonged depolarization is abolished and accompanied by a conformational change in the S4 segment. We propose that the pore influences the voltage sensor by the presence of a ''mechanical load'' and allosterically induces a conformational change in the S4.

To cite this abstract, please use the following information:
Acta Physiologica 2011; Volume 201, Supplement 682 :P260

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