ATP inhibition of a mouse brain large-conductance K+ (mslo) channel variant by a mechanism independent of protein phosphorylation

We investigated the effect of ATP in the regulation of two closely related cloned mouse brain large conductance calcium- and voltage-activated potassium (BK) channel α-subunit variants, expressed in human embryonic kidney (HEK 293) cells, using the excised inside-out configuration of the patch-clam...

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Bibliographic Details
Published in:The Journal of physiology 1999-04, Vol.516 (1), p.45-53
Main Authors: Clark, Alan G., Hall, Sarah K., Shipston, Michael J.
Format: Article
Language:English
Subjects:
Adenosine Diphosphate - metabolism
Adenosine Diphosphate - physiology
Adenosine Triphosphate - analogs & derivatives
Adenosine Triphosphate - pharmacology
Adenylyl Imidodiphosphate - pharmacology
Animals
Brain Chemistry - drug effects
Cattle
Electrophysiology
Humans
Kidney - cytology
Kidney - metabolism
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
Large-Conductance Calcium-Activated Potassium Channels
Mice
Nerve Tissue Proteins - metabolism
Nerve Tissue Proteins - physiology
Patch-Clamp Techniques
Phosphorylation
Potassium Channel Blockers
Potassium Channels, Calcium-Activated
Rapid Report
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Summary:We investigated the effect of ATP in the regulation of two closely related cloned mouse brain large conductance calcium- and voltage-activated potassium (BK) channel α-subunit variants, expressed in human embryonic kidney (HEK 293) cells, using the excised inside-out configuration of the patch-clamp technique. The mB2 BK channel α-subunit variant expressed alone was potently inhibited by application of ATP to the intracellular surface of the patch with an IC 50 of 30 μM. The effect of ATP was largely independent of protein phosphorylation events as the effect of ATP was mimicked by the non-hydrolysable analogue 5′-adenylylimidodiphosphate (AMP-PNP) and the inhibitory effect of ATPγS was reversible. In contrast, under identical conditions, direct nucleotide inhibition was not observed in the closely related mouse brain BK channel α-subunit variant mbr5. Furthermore, direct nucleotide regulation was not observed when mB2 was functionally coupled to regulatory β-subunits. These data suggest that the mB2 α-subunit splice variant could provide a dynamic link between cellular metabolism and cell excitability.
ISSN:0022-3751
1469-7793
DOI:10.1111/j.1469-7793.1999.045aa.x