Glimepiride block of cloned beta-cell, cardiac and smooth muscle K(ATP) channels

Br J Pharmacol. 2001 May;133(1):193-9. doi: 10.1038/sj.bjp.0704062.


1. We examined the effect of the sulphonylurea glimepiride on three types of recombinant ATP-sensitive potassium (K(ATP)) channels. 2. K(ATP) channels share a common pore-forming subunit, Kir6.2, which associates with different sulphonylurea receptor isoforms (SUR1 in beta-cells, SUR2A in heart and SUR2B in smooth muscle). 3. Kir6.2 was coexpressed with SUR1, SUR2A or SUR2B in Xenopus oocytes and macroscopic K(ATP) currents were recorded from giant inside-out membrane patches. Glimepiride was added to the intracellular membrane surface. 4. Glimepiride inhibited Kir6.2/SUR currents by interaction with two sites: a low-affinity site on Kir6.2 (IC(50)= approximately 400 microM) and a high-affinity site on SUR (IC(50)=3.0 nM for SUR1, 5.4 nM for SUR2A and 7.3 nM for SUR2B). The potency of glimepiride at the high-affinity site is close to that observed for glibenclamide (4 nM for SUR1, 27 nM for SUR2A), which has a similar structure. 5. Glimepiride inhibition of Kir6.2/SUR2A and Kir6.2/SUR2B currents, but not Kir6.2/SUR1 currents, reversed rapidly. 6. Our results indicate that glimepiride is a high-affinity sulphonylurea that does not select between the beta-cell, cardiac and smooth muscle types of recombinant K(ATP) channel, when measured in inside-out patches. High-affinity inhibition is mediated by interaction of the drug with the sulphonylurea receptor subunit of the channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electric Conductivity
  • Electrophysiology
  • Female
  • Inhibitory Concentration 50
  • Islets of Langerhans*
  • Mice
  • Muscle, Smooth*
  • Myocardium*
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Potassium Channel Blockers*
  • Potassium Channels / genetics
  • Potassium Channels / metabolism
  • Potassium Channels, Inwardly Rectifying*
  • Rats
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / metabolism
  • Substrate Specificity
  • Sulfonylurea Compounds / chemistry
  • Sulfonylurea Compounds / pharmacology*
  • Xenopus laevis


  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Recombinant Proteins
  • Sulfonylurea Compounds
  • glimepiride