Binding potassium channels

Antidiabetic Drugs other than Insulin. Figure 1 Sulphonylureas stimulate insulin release by pancreatic (3-cells. They bind to the sulphonylurea receptor (SUR-1), which closes Kir6.2 (ATP-sensitive) potassium channels. This promotes depolarisation, voltage-dependent calcium influx, and activation of calcium-sensitive proteins that control exocytotic release of insulin. 

Blaustein, M.P., and Ickowicz, R.K. Phencyclidine in nanomolar concentrations binds to synaptosomes and blocks certain potassium channels. Proc Natl Acad Sci USA 80 3855-3859, 1983. 

While producing the same effect as sulfonylureas, nonsulfonylurea secretagogues, also referred to as meglitinides, have a much shorter onset and duration of action. Nonsulfonylurea secretagogues also produce a pharmacologic effect by interacting with ATP-sensitive potassium channels on the (1-cells however, this binding is to a receptor adjacent to those to which sulfonylureas bind. 

Zhang, S., Zhou, Z., Gong, Q., Makielski, J.C. and January, C.T. (1999) Mechanism of block and identification of the verapamil binding domain to HERG potassium channels. Circulation Research, 84, 989-998. 

Cui, J., Kagan, A., Qin, D., Mathew, J., Melman, Y.F. and McDonald, T.V. (2001) Analysis of the cyclic nucleotide binding domain of the HERG potassium channel and interactions with KCNE2. The Journal of Biological Chemistry, 276, 17244-17251. 

---