The sulphonylurea receptor confers diazoxide sensitivity on the inwardly rectifying K+ channel Kir6.1 expressed in human embryonic kidney cells.
1. We have examined the effects of diazoxide and intracellular ATP (ATPi) on whole-cell currents in HEK293 cells transfected transiently with the inwardly rectifying K+ channel Kir6.1 (uKATP1) or cotransfected with Kir6.1 and the sulphonylurea receptor (SUR1). 2. Kir6.1 currents were unaffected by the K+ channel opener diazoxide or by dialysis with 0.3 mM ATPi. 3. Kir6.1-SUR1 currents increased in amplitude when cells were dialysed with 0.3 mM ATP, but not with 5 mM ATP. This activation may be explained by the loss of endogenous ATP from the cell when the intracellular solution contains 0.3 mM ATP. Kir6.1-SUR1 currents were also activated by diazoxide; this activation was greater with 0.3 mM ATP1 than with 5 mM ATP1. 4. We conclude that SUR1 is required to confer both diazoxide and ATP sensitivity on Kir6.1.
Ammälä
C
C
University Laboratory of Physiology, Oxford, UK.
Moorhouse
A
A
Ashcroft
F M
FM
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D003981:Diazoxide / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D014044:Tolbutamide / Q000494:pharmacology
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D003981:Diazoxide