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Zinc is both an intracellular and extracellular regulator of K ATP channel function
Author(s) -
Prost AnneLise,
Bloc Alain,
Hussy Nicolas,
Derand Renaud,
Vivaudou Michel
Publication year - 2004
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 - 10.1113/jphysiol.2004.065094
Subject(s) - extracellular , activator (genetics) , intracellular , protein subunit , kir6.2 , biophysics , chemistry , biochemistry , microbiology and biotechnology , biology , receptor , gene
Extracellular Zn 2+ has been identified as an activator of pancreatic K ATP channels. We further examined the action of Zn 2+ on recombinant K ATP channels formed with the inward rectifier K + channel subunit Kir6.2 associated with either the pancreatic/neuronal sulphonylurea receptor 1 (SUR1) subunit or the cardiac SUR2A subunit. Zn 2+ , applied at either the extracellular or intracellular side of the membrane appeared as a potent, reversible activator of K ATP channels. External Zn 2+ , at micromolar concentrations, activated SUR1/Kir6.2 but induced a small inhibition of SUR2A/Kir6.2 channels. Cytosolic Zn 2+ dose‐dependently stimulated both SUR1/Kir6.2 and SUR2A/Kir6.2 channels, with half‐maximal effects at 1.8 and 60 μ m , respectively, but it did not affect the Kir6.2 subunit expressed alone. These observations point to an action of both external and internal Zn 2+ on the SUR subunit. Effects of internal Zn 2+ were not due to Zn 2+ leaking out, since they were unaffected by the presence of a Zn 2+ chelator on the external side. Similarly, internal chelators did not affect activation by external Zn 2+ . Therefore, Zn 2+ is an endogenous K ATP channel opener being active on both sides of the membrane, with potentially distinct sites of action located on the SUR subunit. These findings uncover a novel regulatory pathway targeting K ATP channels, and suggest a new role for Zn 2+ as an intracellular signalling molecule.