Potassium channel opener explained

A potassium channel opener is a type of drug which facilitates ion transmission through potassium channels.

Examples

Some examples include:

• Diazoxide^[1] vasodilator used for hypertension, smooth muscle relaxing activity
• Minoxidil^[2] vasodilator used for hypertension, also used to treat hair loss
• Nicorandil^[3] vasodilator used to treat angina
• Pinacidil^[4]
• Retigabine,^{[5] [6]} an anticonvulsant
• Flupirtine, analgesic with muscle relaxant and anticonvulsant properties

Class	Subclasses	Activators
Calcium-activated 6T & 1P	BK channel SK channel IK channel	1-EBIO NS309 CyPPA BKCa-specific: Flufenamic acid Meclofenamic acid Niflumic acid Nimesulide Rottlerin (mallotoxin) Tolfenamic acid
Inwardly rectifying 2T & 1P	ROMK (Kir1.1)	none
	GPCR regulated (Kir3.x)	GPCR agonists ML-297 (VU0456810)
	ATP-sensitive (Kir6.x)	Aprikalim Bimakalim Cromakalim Diazoxide Emakalim Levcromakalim Mazokalim Minoxidil Naminidil Nicorandil Pinacidil Rilmakalim Sarakalim
Tandem pore domain 4T & 2P	TWIK (TWIK-1, TWIK-2, KCNK7)^[7] ^[8] TREK (TREK-1, TREK-2, TRAAK^[9]) TASK (TASK-1, TASK-3, TASK-5) TALK (TASK-2,^[10] TALK-1, TALK-2) THIK (THIK-1, THIK-2) TRESK^[11] ^[12]	halothane^[13] ^[14] ^[15] Riluzole Arachidonic acid
Voltage-gated 6T & 1P	hERG (Kv11.1) KvLQT1 (Kv7.1)	KCNQ (Kv7)-specific: Flupirtine Retigabine (Kv7)^[16] XEN1101^[17]

See also

• Potassium channel blocker

Notes and References

1. Mizutani S, Prasad SM, Sellitto AD, Schuessler RB, Damiano RJ, Lawton JS. August 2005. Myocyte volume and function in response to osmotic stress: observations in the presence of an adenosine triphosphate-sensitive potassium channel opener. Circulation. 112. 9 Suppl. I219–23. 10.1161/CIRCULATIONAHA.104.523746. 16159820. free.
2. Wang T. February 2003. The effects of the potassium channel opener minoxidil on renal electrolytes transport in the loop of henle. J. Pharmacol. Exp. Ther.. 304. 2. 833–40. 10.1124/jpet.102.043380. 12538840. 6948410.
3. Sudo H, Yogo K, Ishizuka N, Otsuka H, Horie S, Saito K. November 2008. Nicorandil, a potassium channel opener and nitric oxide donor, improves the frequent urination without changing the blood pressure in rats with partial bladder outlet obstruction. Biol. Pharm. Bull.. 31. 11. 2079–82. 10.1248/bpb.31.2079. 18981577. free.
4. Stojnic N, Gojkovic-Bukarica L, Peric M, etal. June 2007. Potassium channel opener pinacidil induces relaxation of the isolated human radial artery. J. Pharmacol. Sci.. 104. 2. 122–9. 10.1254/jphs.FP0061434. 17538231. free.
5. Rundfeldt C. October 1997. The new anticonvulsant retigabine (D-23129) acts as an opener of K+ channels in neuronal cells. European Journal of Pharmacology. 336. 2–3. 243–9. 10.1016/S0014-2999(97)01249-1. 9384239.
6. Main MJ, Cryan JE, Dupere JR, Cox B, Clare JJ, Burbidge SA. August 2000. Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine. Molecular Pharmacology. 58. 2. 253–62. 10.1124/mol.58.2.253. 10908292. 11112809 .
7. Enyedi P, Czirják G. Apr 2010. Molecular background of leak K+ currents: two-pore domain potassium channels. Physiological Reviews. 90. 2. 559–605. 10.1152/physrev.00029.2009. 20393194. 9358238.
8. Lotshaw DP. 2007. Biophysical, pharmacological, and functional characteristics of cloned and native mammalian two-pore domain K+ channels. Cell Biochemistry and Biophysics. 47. 2. 209–56. 10.1007/s12013-007-0007-8. 17652773. 12759521.
9. Fink M, Lesage F, Duprat F, Heurteaux C, Reyes R, Fosset M, Lazdunski M. Jun 1998. A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids. The EMBO Journal. 17. 12. 3297–308. 10.1093/emboj/17.12.3297. 1170668. 9628867.
10. Goldstein SA, Bockenhauer D, O'Kelly I, Zilberberg N. Mar 2001. Potassium leak channels and the KCNK family of two-P-domain subunits. Nature Reviews. Neuroscience. 2. 3. 175–84. 10.1038/35058574. 11256078. 9682396.
11. Sano Y, Inamura K, Miyake A, Mochizuki S, Kitada C, Yokoi H, Nozawa K, Okada H, Matsushime H, Furuichi K. Jul 2003. A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord. The Journal of Biological Chemistry. 278. 30. 27406–12. 10.1074/jbc.M206810200. 12754259. 22656809. free.
12. Czirják G, Tóth ZE, Enyedi P. Apr 2004. The two-pore domain K+ channel, TRESK, is activated by the cytoplasmic calcium signal through calcineurin. The Journal of Biological Chemistry. 279. 18. 18550–8. 10.1074/jbc.M312229200. 14981085. 21219622. free.
13. Meadows HJ, Randall AD. Mar 2001. Functional characterisation of human TASK-3, an acid-sensitive two-pore domain potassium channel. Neuropharmacology. 40. 4. 551–9. 10.1016/S0028-3908(00)00189-1. 11249964. 20181576.
14. Patel AJ, Honoré E, Lesage F, Fink M, Romey G, Lazdunski M. May 1999. Inhalational anesthetics activate two-pore-domain background K+ channels. Nature Neuroscience. 2. 5. 422–6. 10.1038/8084. 10321245. 23092576.
15. Gray AT, Zhao BB, Kindler CH, Winegar BD, Mazurek MJ, Xu J, Chavez RA, Forsayeth JR, Yost CS. Jun 2000. Volatile anesthetics activate the human tandem pore domain baseline K+ channel KCNK5. Anesthesiology. 92. 6. 1722–30. 10.1097/00000542-200006000-00032. 10839924. 45487917.
16. Rogawski MA, Bazil CW. Jul 2008. New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7/KCNQ/M potassium channels. Current Neurology and Neuroscience Reports. 8. 4. 345–52. 10.1007/s11910-008-0053-7. 2587091. 18590620.
17. Premoli I, Rossini PG, Goldberg PY, Posadas K, Green L, Yogo N, Pimstone S, Abela E, Beatch GN, Richardson MP . TMS as a pharmacodynamic indicator of cortical activity of a novel anti-epileptic drug, XEN1101 . Annals of Clinical and Translational Neurology . 6 . 11 . 2164–2174 . November 2019 . 31568714 . 6856596 . 10.1002/acn3.50896 . XEN1101 is a novel positive allosteric modulator (“opener”) of the potassium channel KCNQ2/3 (Kv7.2/7.3) currently being developed by Xenon Pharmaceuticals Inc. for the treatment of focal epilepsy..