Deletion of cytosolic gating ring decreases gate and voltage sensor coupling in BK channels

作者：Zhang, Guohui; Geng, Yanyan; Jin, Yakang; Shi, Jingyi; McFarland, Kelli; Magleby, Karl L.; Salkoff, Lawrence; Cui, Jianmin^*

来源：Journal of General Physiology, 2017, 149(3): 373-387.

DOI：10.1085/jgp.201611646

• ACTIVATED POTASSIUM CHANNELS
• CA2+-ACTIVATED K+ CHANNEL
• SACCULAR HAIR-CELLS
• BETA-SUBUNIT
• STRUCTURAL BASIS
• IONIC CURRENTS
• CA2+ BINDING
• BULL-FROG
• CALCIUM
• CONDUCTANCE

Large conductance Ca2+-activated K+ channels (BK channels) gate open in response to both membrane voltage and intracellular Ca2+. The channel is formed by a central pore-gate domain (PGD), which spans the membrane, plus transmembrane voltage sensors and a cytoplasmic gating ring that acts as a Ca2+ sensor. How these voltage and Ca2+ sensors influence the common activation gate, and interact with each other, is unclear. A previous study showed that a BK channel core lacking the entire cytoplasmic gating ring (Core-MT) was devoid of Ca2+ activation but retained voltage sensitivity (Budelli et al. 2013. Proc. Natl. Acad. Sci. USA. http://dx.doi.org/10.1073/pnas.1313433110).In this study, we measure voltage sensor activation and pore opening in this Core-MT channel over a wide range of voltages. We record gating currents and find that voltage sensor activation in this truncated channel is similar to WT but that the coupling between voltage sensor activation and gating of the pore is reduced. These results suggest that the gating ring, in addition to being the Ca2+ sensor, enhances the effective coupling between voltage sensors and the PGD. We also find that removal of the gating ring alters modulation of the channels by the BK channel's beta 1 and beta 2 subunits.

• 出版日期2017-3
• 单位苏州大学