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ATP inhibition of a mouse brain large‐conductance K + (mslo) channel variant by a mechanism independent of protein phosphorylation
Author(s) -
Clark Alan G.,
Hall Sarah K.,
Shipston Michael J.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.045aa.x
Subject(s) - phosphorylation , protein subunit , g alpha subunit , hek 293 cells , bk channel , intracellular , patch clamp , microbiology and biotechnology , chemistry , potassium channel , biophysics , protein kinase a , biology , biochemistry , gene , receptor
1 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. 2 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. 3 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. 4 These data suggest that the mB2 α‐subunit splice variant could provide a dynamic link between cellular metabolism and cell excitability.