Potassium channels cardiac

Nicorandil. Nicorandil is a potassium channel opener that can lower blood pressure 21, 20, and 29 mm Hg after single oral doses of 10, 20, and 30 mg, respectively (250). There are no significant changes ia heart rate. Headache is the primary side effect. Nicorandil has potent coronary vasodilator effects. It causes sustained vasodilation of arteriolar resistance and venous capacitance blood vessels, thus reduciag cardiac preload and aftedoad. 

Shaker-channels, eag (ether- -go-go)-channels, slo (slow-poke)-channels were cloned from behavioral Drosophila melanogaster mutants. The channels were named according to the Drosophila mutant phenotype, Shaker, ether-go-go, slow-poke. Subsequently, eag-cDNA was used to clone related voltage-gated potassium channel subunits erg (eag-related) and elk (eag-like). The human erg ortholog (HERG) mediates cardiac DCS. 

Vandeberg, C.A. (1987). Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions. Proc. Natl Acad. Sci. USA 84, 2560-2564. 

Sun, H. Liu, X. Xiong, Q. Shikano, S. Li, M. Chronic inhibition of cardiac Kir2.1 and hERG potassium channel by celastrol with dual effects on both ion conductivity and protein trafficking. J. Biol. Chem. 2006, 281, 5877-5884. 

FIGURE 7.14 Time-course of G-protein-mediated activation of GIRK potassium channels in rabbit sinoatrial node cells, (a). Outward current evoked by a 33-msec, 50-nA iontophoretic pulse of acetylcholine (between arrows), (b). Response of the unclamped cell to an iontophoretic pulse of acetylcholine (ACh). (Record (a) is adapted with permission from Trautwein et al., in Drug Receptors and Their Effectors, Birdsall, N. J. M., Ed., Macmillan, New York, 1980, pp. 5-22 record (b) is adapted with permission from Noma, in Electrophysiology of Single Cardiac Cells, Noble, D. and Powell, T., Eds., Academic Press, San Diego, CA, 1987, pp. 223-246.)... 

Cardiac Action Potential In Vitro Purkinje Fibers. Intracellular recording of action potentials from cardiac Purkinje fibers isolated from dog or sheep ventricle. Measurement of maximum rate of depolarization and action potential duration to detect sodium and potassium channel interactions, respectively, according to recommendations in EM A CPMP Points to Consider document, CPMP 986/96 (1998). 

Shivkumar, K. and Valderrabano, M. (2004) Use of potassium channel openers for pharmacologic modulation of cardiac excitability. Journal of Cardiovascular Electrophysiology, 15, 821-823. 

Roden, D.M. and George, A.L.J. (1997) Structure and function of cardiac sodium and potassium channels. The American Journal of Physiology, 273, H511-H525. 

W., Keating, M.T. and Goldstein, S.A. (1999) MiRPl forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell, 97, 175-187. 

Lacerda, A.E., Kramer, J., Shen, K.Z., Thomas, D. and Brown, A.M. (2001) Comparison of block among cloned cardiac potassium channels by non-antiarrhythmic drugs. European Heart Journal Supplements, 3, K23-K30. 

Sanguinetti, M.C., Jiang, C., Curran, M.E. and Keating, M.T. (1995) A mechanistic linkbetween an inherited and an acquired cardiac arrhythmia HERG encodes the Iki potassium channel. Cell, 81, 299-307. 

Sanguinetti, M.C. and Tristani-Firouzi, M. (2006) hERG potassium channels and cardiac arrhythmia. Nature, 440, 463 69. 

Ficker, E., Dennis, A.T., Wang, L. and Brown, A.M. (2003) Role of the cytosolic chaperones Hsp70 and Hsp90 in maturation of the cardiac potassium channel HERG. Circulation Research, 92, e87-100. 

The ability of a molecule to bind to the potassium channel, hERG (human ether-a-go-go related gene), is a serious pharmacological concern and may lead to the failure to progress an otherwise active and druglike molecule during the lead optimization process. Cardiac QT interval prolongation has been associated to some extent with... 

Tse, H.-F., Zhang, S. and Li, G.-R. (2008) The 5-HT2 antagonist ketanserin is an open channel blocker of human cardiac ether-a-go-go-related gene (hERG) potassium channels. British Journal of Pharmacology, 81, 1-9. 

Safety pharmacology In vitro assays can test for hERG potassium channel interaction early in discovery, with ox vivo and in vivo assays being applied later in discovery. HCA assays are being developed for in vitro assessments of cardiac toxicity potential... 

Other potassium channels also play important roles here. For example, Kv4.3/ KChIP complex conducts the transient outward current, Ito, responsible for the descending phase 1 of the cardiac action potential, whereas Kvl.5 is underlying the ultra rapid delayed rectifying current, IKur, responsible for descending phase 2. Finally, inward rectifier potassium channel (Kir2 family) is responsible for IKl current, which maintains the action potential close to or at the resting level (phase 4). 

Diazoxide is a potassium channel opener with a rapid antihypertensive action after intravenous administration. Diazoxide causes hyperglycaemia which may underlie side-effects such as nausea and vomiting, cardiac dysrhythmia and ketosis. Diazoxide was used occasionally in the management of hypertensive emergencies, but it is now largely abandoned for this indication. Diazoxide is an alternative for glucagons in patients with hypogycaemia. 

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