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Published on: January 10, 2011
Tuning the gate and the gear: The LRRC26 ( γ 1 ) subunit modulates intrinsic gating and voltage-sensor coupling of
Felipe Echeverria1,2, Antonio Peña-Pichicoi1, Miguel Fernandez1
1Centro Interdisciplinario de Neurociencia. Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso Pasaje Harrington 287, Valparaíso 2340000, Chile.
Abstract:
Association of auxiliary subunits ( and ) with the pore-forming subunit of the calcium-and voltage-activated potassium (BK) channel provides functional diversity. promotes a significant leftward shift of the voltage activation curve, ensuring the adequate functioning of secretory glands, allowing the BK channel to release at the cell's resting concentration. Given its physiological importance, it is crucial to elucidate the mechanisms of action. However, structural and functional studies have yielded conflicting conclusions regarding the modulation of BK channels by . Here, using macroscopic, single-channel, and gating current measurements, we demonstrate that at zero mV increases 92-fold the equilibrium constant that defines the closed-open transition by destabilizing the channel's closed configuration and enhancing the coupling between the voltage sensor and the pore domain, without affecting voltage-sensor activation. These results suggest that not only causes an increase in the energetic coupling between the voltage sensors and the pore but mainly enhances the channel opening reaction.
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