Cl. Lawrence et al., Gliclazide produces high-affinity block of K-ATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells, DIABETOLOG, 44(8), 2001, pp. 1019-1025
Aims/hypothesis. Sulphonylureas stimulate insulin secretion by closing ATP-
sensitive potassium (K-ATP) channels in the pancreatic beta-cell membrane.
K-ATP channels are also found in other tissues, including heart and smooth
muscle, where they link cellular metabolism to electrical activity. The sul
phonylurea gliclazide blocks recombinant beta-cell K-ATP channels (Kir6.2/S
UR1) but not heart (Kir6.2/SUR2A) or smooth muscle (Kir6.2/SUR2B) K-ATP cha
nnels with high potency. In this study, we examined the specificity of glic
lazide for the native (as opposed to recombinant) K-ATP channels in beta ce
lls, heart and smooth muscle.
Methods. The action of the drug was studied by whole-cell current recording
s of native K-ATP channels in isolated pancreatic beta-cells and myocytes f
rom heart and smooth muscle.
Results. Gliclazide blocked whole-cell beta-cell K-ATP currents with an IC5
0 of 184 +/- 30 nmol/l (n = 6-10) but was much less effective in cardiac an
d smooth muscle (IC(50)s of 19.5 +/- 5.4 mu mol/l (n = 6-12) and 37.9 +/- 1
.0 mu mol/l (n = 5-10), respectively). In all three tissues, the action of
the drug on whole-cell K-ATP currents was rapidly reversible. In inside-out
patches on beta-cells, gliclazide (1 mu mol/1) produced a maximum of 66 +/
- 13% inhibition (n = 5), compared with more than 98% block in the whole-ce
Conclusion/interpretation. Gliclazide is a high-potency sulphonylurea which
shows specificity for the pancreatic beta-cell K-ATP channel over heart an
d smooth muscle. In this respect, it differs from glibenclamide. The differ
ence in the maximal block observed in the excised patch and whole-cell reco
rdings from beta-cells, may be due to the absence of intracellular Mg-nucle
otides in the excised patch experiments.