BK channel inhibition by strong extracellular acidification.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29963986.
- Also identified by DOI 10.7554/eLife.38060 and PMC identifier 6054526.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Mammalian BK-type voltage- and Ca<sup>2+</sup>-dependent K<sup>+</sup> 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<sup>+</sup>, with its conductance-voltage relationship shifted by more than +100 mV at pH<sub>O</sub> 4. Our results reveal that this inhibition is mainly caused by H<sup>+</sup> 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.
Medical subject headings
- Aspartic Acid
- Calcium
- Intracellular Membranes
- Large-Conductance Calcium-Activated Potassium Channel alpha Subunits