TY - JOUR
T1 - BK channel inhibition by strong extracellular acidification
AU - Zhou, Yu
AU - Xia, Xiao Ming
AU - Lingle, Christopher J.
N1 - Funding Information:
This work was supported by NIH grant GM118114 to CJL.
Funding Information:
This work was supported by NIH grant GM118114 to CJL. National Institute of General Medical Sciences GM118114 Christopher J Lingle.
Publisher Copyright:
© Zhou et al.
PY - 2018/7/2
Y1 - 2018/7/2
N2 - Mammalian BK-type voltage- and Ca 2+ -dependent K + channels are found in a wide range of cells and intracellular organelles. Among different loci, the composition of the extracellular microenvironment, including pH, may differ substantially. For example, it has been reported that BK channels are expressed in lysosomes with their extracellular side facing the strongly acidified lysosomal lumen (pH ~4.5). Here we show that BK activation is strongly and reversibly inhibited by extracellular H + , with its conductance-voltage relationship shifted by more than +100 mV at pHO 4. Our results reveal that this inhibition is mainly caused by H+ inhibition of BK voltage-sensor (VSD) activation through three acidic residues on the extracellular side of BK VSD. Given that these key residues (D133, D147, D153) are highly conserved among members in the voltage-dependent cation channel superfamily, the mechanism underlying BK inhibition by extracellular acidification might also be applicable to other members in the family.
AB - Mammalian BK-type voltage- and Ca 2+ -dependent K + channels are found in a wide range of cells and intracellular organelles. Among different loci, the composition of the extracellular microenvironment, including pH, may differ substantially. For example, it has been reported that BK channels are expressed in lysosomes with their extracellular side facing the strongly acidified lysosomal lumen (pH ~4.5). Here we show that BK activation is strongly and reversibly inhibited by extracellular H + , with its conductance-voltage relationship shifted by more than +100 mV at pHO 4. Our results reveal that this inhibition is mainly caused by H+ inhibition of BK voltage-sensor (VSD) activation through three acidic residues on the extracellular side of BK VSD. Given that these key residues (D133, D147, D153) are highly conserved among members in the voltage-dependent cation channel superfamily, the mechanism underlying BK inhibition by extracellular acidification might also be applicable to other members in the family.
UR - http://www.scopus.com/inward/record.url?scp=85052238517&partnerID=8YFLogxK
U2 - 10.7554/eLife.38060
DO - 10.7554/eLife.38060
M3 - Article
C2 - 29963986
AN - SCOPUS:85052238517
VL - 7
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e38060
ER -