Potassium channels diseases

CFTR has a single-channel conductance of about 8 pS. It is present in the apical membranes of many epithelia. Its mutation leads to the potentially lethal disease cystic fibrosis. In addition to acting as a chloride channel, CFTR is also thought to regulate, e.g., the epithelial sodium channel ENaC, a molecularly unknown outwardly-rectifying chloride channel, and possibly also potassium channels and water channels. Some of these potential regulatory processes, however, are controversial. CFTR also acts as a receptor for bacteria. 

Shieh CC, Coghlan M, Sullivan JP et al (2000) Potassium channels molecular defects, diseases, and therapeutic opportunities. Pharmacol Rev 52 557-594... 

Jentsch TJ (2000) Neuronal KCNQ potassium channels physiology and role in disease. Nat Rev Neurosci 1 21-30... 

The Vaughan-Williams classification of antiarrhythmic drugs has been criticized for a number of reasons. The classification is based on the effects of drugs on normal, rather than diseased, myocardium. In addition, many of the drugs may be placed into more than one class. For example, the class IA drugs prolong repolarization/refractoriness, either via the parent drug8,9 or an active metabolite,10 and therefore also maybe placed in class III. Sotalol is also a 3-blocker, and therefore fits into class II. Amiodarone inhibits sodium and potassium channels, is a non-competitive inhibitor of 3-receptors, and inhibits calcium... 

Sobey CG. (2001) Potassium channel function in vascular disease. Arterioscler Thromb Vase Biol 21 28-38. 

ICA -17043 is a novel inhibitor of the Gardos channel (a calcium-dependent potassium channel). This drug is indicated for the treatment of a hematologic genetic disease (sickle cell disease) (Phase 11) (Figure 8.88). 

Ion channel modulation represents another approach to positive inotropy [13]. Sodium channel modulators increase Na+ influx and prolong the plateau phase of the action potential sodium/calcium exchange then leads to an increase in the level of calcium available to the contractile elements, thus increasing the force of cardiac contraction [13,14]. Synthetic compounds such as DPI 201-106 and BDF 9148 (Figure 1) increase the mean open time of the sodium channel by inhibiting channel inactivation [15]. Importantly, BDF 9148 remains an effective positive inotropic compound even in severely failing human myocardium [16] and in rat models of cardiovascular disease [17]. Modulators of calcium and potassium channel activities also function as positive inotropes [13], but in the remainder of this article we shall focus on sodium channel modulators. 

Epilepsy may arise also from defects in a GABA transporter1145 or receptor.1146 One form of epilepsy is a triple-repeat disease of cystatin B (Table 26-4). Mutation in potassium channels,1147 glutamate receptors,1148 absence of neuropeptide Y,1149 and absence of L-isoaspartyl / D-aspartyl O-methyltransferase (Box 12-A)1150 have all been associated with epilepsy. 

Antihypertensive Agents. Hypertension (high blood pressure) is a significant risk factor for cardiovascular diseases such as angina heart attacks, and strokes. /(-Adrenoceptor (adrenergic nervous system receptors of the /(-type) antagonists (/(-blockers), calcium channel blockers, angiotensinconverting enzyme (ACE) inhibitors, and potassium channel activators... 

Fluoro-2-oxindole derivatives, (IV), prepared by Dworetzky (5) were effective modulators of KCNQ potassium channels and used in treating migraine and mechanistically related disease. 

Sour taste detects acids, i.e., protons. Several different sour taste receptor candidates such as acid-sensing ion channels (ASICs) (57), hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) (58), and two pore domain potassium channels (K2PS) (59, 60) have been described in the past. In addition, recent research identified two members of the polycystic kidney disease (PKD) family of the transient receptor potential superfamily (TRP) as strong sour taste receptor candidates or as part thereof. Immunohistochemistry and in situ hybridization revealed the presence of the polycystic-kidney-disease-like ion channel PKD2L1 in subsets of taste receptor cells of mouse fungiform, vallate, and foliate papillae. These cells differ from... 

Small, RC., Berry, J.L., Cook, S.J., Foster, RW., Green, K.A. and Murray, M.A. (1993). Potassium channels in airways. In Lung Biology in Health and Disease. Vol. 67. Pharmacology of the Respiratory Tract Experimental and Clinical Research (eds K.F. Chung and P.J. Barnes), Marcel Dekker, New York. 

Tacrine has numerous mechanisms of action. The putative principle mechanism of action of tacrine for Alzheimer s disease is reversible inhibition of acetylcholinesterase (AChE), which thereby slows the breakdown of the chemical messenger acetylcholine (ACh) in the brain. In addition, tacrine blocks the sodium and potassium channels. 

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