Channeling defects

Felix R Channelopathies ion channel defects linked to heritable clinical disorders. J Med Genet 2000 37 729. 

Fletcher, CF, Lutz, CM, O Sullivan, TN, Shaughnessy Jr, JD, Hawkes, R, Frankel, WN, Copeland, NG and Jenkins, NA (1996) Absence epilepsy in tottering mutant mice is associated with calcium channel defects. Cell 87 607-617. 

Cystic fibrosis is a life-threatening genetic disease caused by a dysfunctional cystic fibrosis transmembrane regulator, CFTR protein, which modulates salt and water transport into and out of cells. This ion-channel defect leads to poorly hydrated, thick, mucous secretions in the airways and severely impaired mucociliary func-... 

Pseudoaldosteronism (Liddle s syndrome) Na+ channel defect SCNN1BSCNN1G 16pl3-pl2 16pl3-pl2 600760 600761(177200)... 

Pseudohypoaldosteronism, PHA-I Sodium channel defect or MR mutation SCNN1A SCNN1B MR 12pl3 16pl3-pl2 600228 600760... 

TABLE 11-8 Some Diseases Resulting from Ion Channel Defects... 

Lehmann-Horn, F. Jurkat-Rott, K. (1999) Voltage-gated ion channels and hereditary disease. Physiol. Rev. 79, 1317-1372. Advanced review of the structure and function of ion channels, with special emphasis on cases in which ion-channel defects produce human diseases. 

Correction of the chloride channel defect in cells explanted from CF patients by the introduction of the normal CFTR cDNA suggests that gene therapy may be beneficial. It may be sufficient to deliver the normal cDNA just to the respiratory epithelial cells. A number of strategies for gene therapy by using viral vectors and other delivery methods are under development and are being tested (Collins, 1992). These approaches are discussed in detail in Chapter 6. 

Cannon SC, Brown RH Jr, Corey DP. A sodium channel defect in hyperkalemic periodic paralysis potassium-induced failure of inactivation. Neuron 1991 6 619-626. 

Segal There are a variety of clinical syndromes with congenital insensitivity to pain. Have people looked at these for channel defects ... 

Cystic fibrosis is a hereditary disorder caused by mutation in the cystic fibrosis transmembrane conductance regulator gene that encodes a cyclic adenosine monophosphate-regulated chloride channel. Defects in chloride ion transport in the airway epithelia lead to abnormal airway secretions, impaired mucociliary clearance, chronic bacterial infection, bronchiectasis, and premature death. Delivery of the cystic fibrosis transmembrane conductance regulator cDNA by adenovirus vectors or the plasmid-liposome complex resulted in transient correction of the defects in patients with cystic fibrosis. Formulations of cationic lipid-DNA complexes for aerosol delivery are being explored to improve on the gene therapy approach. 

Syndrome Channel Defect Mutant Gene Characteristics Treatment... 

Lerche H, Weber YG, Jurkat-Rott K, et al. Ion channel defects in idiopathic epilepsies. Curr Pharm Des 2005 11 2737-2752. 

Fertleman CR, Baker MD, Parker KA, Moffatt S, Elmslie FV, Abrahamsen B, Ostman J, Klugbauer N, Wood JN, Gardiner RM, Rees M (2006) SCN9A mutations in paroxysmal extreme pain disorder Allelic variants underlie distinct channel defects and phenotypes. Neuron... 

Figure 16.27. A classical lamellar arrangement of bilayers (a) containing (b) a puncture defect and (c) a channel defect...

Fig. 12. Model for apolipoprotein phospholipid association. In the left panel, the surface of a phospholipid-.cholesterol vesicle is depicted as a biphasic system in which homogeneous DMPC and 1 3 cholesterol-DMPC phases coexist. Each phase is bonded by interfacial lipid, and the interfacial lipid of each phase is separated from that of the other phase by a hole or channel defect. ApoA-I may insert into this defect to produce the initial lipid apoprotein intermediate on the right. The apoprotein is envisioned as a helical structure in the lipid matrix (from Pownall et al., 1979a).

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