Research over the past 10 years has produced remarkable advances in our understanding of the structure and function of ion channels. One fringe benefit of this work has been the recognition that mutations in the genes encoding skeletal muscle sodium, calcium, and chloride channels share responsibility for a group of inherited disorders that affect muscle membrane excitability (see Ref. 1 for review). The phenotype of these disorders ranges from membrane hyperexcitability (myotonia) to inexcitability (episodic paralysis). Unfortunately, molecular analysis of these disorders has not yielded a neat correlation between phenotype and genotype. The nosologic waters have been muddied by the fact that mutations at different locations in the same gene can produce either a paralytic or a myotonic phenotype, while mutations in different channel genes can lead to phenotypes that appear clinically indistinguishable. In an article in this issue, 13 Wagner et al. address the reliability of fluctuations in the severity of myotonia as an indicator of the underlying channel defect in patients with dominant myotonia congenita.

Muscle stiffness is the predominant symptom in the dominant and recessive forms of myotonia congenita. Through the pioneering work of Bryant and his coworkers, 2 the symptoms in this disease and its hereditary counterpart in goats have been linked to an abnormally high muscle membrane resistance that results from a reduction in sarcolemmal chloride conductance (GCl). Chloride ion movement through this pathway normally represents∼ 70% of the resting membrane conductance in muscle10 and stabilizes the surface membrane potential during the fluctuations in T-tubular potassium level that occur with muscle activity. Most families with dominant or recessive myotonia congenita have been found to