The muscle membrane in myotonia congenita is characterized by a normal resting potential with a greatly increased resting resistance usually attributed to a decrease in membrane chloride permeability (Pcl). In this report, the hypothesis that decreased Pcl alone can account for the repetitive action potentials of myotonia is tested with a mathematical model of the muscle membrane and is shown to be valid. Reduction of Pcl to 20% of control values will produce myotonic activity in response to a single stimulus. Membrane resistance and potential approximate those found experimentally. The model predicts that increasing external K+ will aggravate myotonia due to a reduction of Pcl, while decreasing Kout will prevent repetitive spiking. Further, myotonia can be prevented by reducing peak membrane sodium permeability or by shifting the voltage dependency of the membrane rate constants for sodium in a depolarizing direction. These results are shown to correlate well with clinical observation and provide explanations for the action of drugs effective in the treatment of myotonia.
Barchi RL. MyotoniaAn Evaluation of the Chloride Hypothesis. Arch Neurol. 1975;32(3):175-180. doi:10.1001/archneur.1975.00490450055007