Figure 9. Voluntary contraction in myotonia congenita triggers a sequential progression through states of hyperexcitability and inexcitability.

Shown on the left is a motor unit consisting of a motor neuron and the muscle fibers it innervates. At rest, both the motor neuron and muscle fibers are hyperpolarized and muscle is relaxed. To initiate voluntary contraction, the motor neuron fires repeated action potentials, which activate the neuromuscular junction (NMJ) to trigger repeated firing of action potentials in muscle (indicated by a yellow outline around the fiber). With the rapid firing of muscle action potentials, there is sustained contraction and force production (blue line). At the end of voluntary contraction, the motor neuron stops firing and the NMJ repolarizes, but in myotonic muscle there is continued involuntary firing of action potentials, which slows relaxation of muscle. When myotonia is terminated by transition into a plateau potential, muscle remains depolarized but cannot fire action potentials (black outline of the fiber), such that muscle is paralyzed. Finally, there is sudden repolarization and return of muscle to the resting state. Under the voltage trace our hypothesis regarding the contribution of NaPIC and current through Ca_V1.1 channels is illustrated. NaPIC begins to turn on at the end of voluntary contraction and triggers myotonia. In some runs of myotonia, NaPIC continues to increase and contributes to initiation of plateau potentials. The initial plateau potential voltage is sufficiently depolarized to trigger opening of Ca_V1.1 channels, which help to sustain plateau potentials. The gradual repolarization during plateau potentials causes Ca_V1.1 channels to close prior to termination of the potential. Rapid, voltage-dependent closing of Na⁺ channels in the NaPIC mode contributes to termination of plateau potentials. ACh = acetylcholine.