The ATP- and tolbutamide-sensitivity of the ATP-sensitive K-channel from human pancreatic B cells.
The ATP- and sulphonylurea-sensitivity of the ATP-sensitive K-channel was measured in human pancreatic B cells. In inside-out patches, half-maximal inhibition of channel activity was produced by 10 mumol/l ATP (with 2 mM Mg2+) and ATP-inhibition was partially antagonised by ADP. A significantly lower sensitivity to ATP was found in whole-cell recordings. Tolbutamide inhibited whole-cell ATP-sensitive K-currents half-maximally at 18 mumol/l; the sensitivity to tolbutamide was somewhat less in the inside-out patch. Ca-activated K-channels were unaffected by tolbutamide (10 mmol/l). These results resemble those found for rodent B cells and suggest that sulphonylureas exert their therapeutic effects in Type 2 (non-insulin dependent) diabetes by inhibition of the ATP-sensitive K-channel.
Ashcroft
F M
FM
University Laboratory of Physiology, John Radcliffe Hospital, Oxford, UK.
Kakei
M
M
Gibson
J S
JS
Gray
D W
DW
Sutton
R
R
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D014044:Tolbutamide / Q000494:pharmacology*
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D002118:Calcium