Ion Channels as Targets for Genetic Disease

Publisher Summary Ion channels are targets of disease, either directly through a mutation in the gene coding for some critical part of the channel protein structure or indirectly, through autoimmune disease or by defective coding of a critical ion channel regulator. This chapter illustrates examples to explain each case. When ion channel function is abnormal, malfunction of excitable cells are seen, as shown in the myotonias or periodic paralysis, or problems with ion transport, as shown in cystic fibrosis and malignant hyperthermia. No region of the channel protein is immune to the effects of mutation. Effects are seen on gating, selectivity, and unit conductance. Often a change in a single amino acid accounts for the altered function of a channel or of its regulator. Modern electrophysiological methods, including the patch clamp, have made the monitoring of channel function very direct and convenient. Combining the new electrophysiology with the new molecular biology has been successful in offering a staggering amount of information on normal and diseased channels in a remarkably short period of time.