Subtype-specific, bi-component inhibition of SK channels by low internal pH.
Research output: Contribution to journal › Journal article › Research › peer-review
The effects of low intracellular pH (pH(i) 6.4) on cloned small-conductance Ca2+-activated K+ channel currents of all three subtypes (SK1, SK2, and SK3) were investigated in HEK293 cells using the patch-clamp technique. In 400 nM internal Ca2+ [Ca2+]i, all subtypes were inhibited by pH(i) 6.4 in the order of sensitivity: SK1>SK3>SK2. The inhibition increased with the transmembrane voltage. In saturating internal Ca2+, the inhibition was abolished for SK1-3 channels at negative potentials, indicating a [Ca2+]i-dependent mode of inhibition. Application of 50 microM 1-ethyl-2-benzimidazolone was able to potentiate SK3 current to the same extent as at neutral pH(i). We conclude that SK1-3 all are inhibited by low pH(i). We suggest two components of inhibition: a [Ca2+]i-dependent component, likely involving the SK beta-subunits calmodulin, and a voltage-dependent component, consistent with a pore-blocking effect. This pH(i)-dependent inhibition can be reversed pharmacologically.
Original language | English |
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Journal | Biochemical and Biophysical Research Communications |
Volume | 343 |
Issue number | 3 |
Pages (from-to) | 943-9 |
Number of pages | 6 |
ISSN | 0006-291X |
DOIs | |
Publication status | Published - 2006 |
Bibliographical note
Keywords: Animals; Benzimidazoles; Calcium; Cell Line; Electric Conductivity; Humans; Hydrogen-Ion Concentration; Patch-Clamp Techniques; Rats; Small-Conductance Calcium-Activated Potassium Channels
ID: 8418707