Physiology of Abnormal Muscle Fiber Generators

Abnormal spontaneous single muscle fiber generators (ASMFGs) in skeletal muscle are characterized in electrodiagnostic medicine (EDM) as: increased insertional activity (IncrIA), fibrillation potentials (FPs: triphasic and biphasic spike forms and the positive sharp wave [PSW] configuration), complex repetitive discharges (CRDs), and myotonic discharges (MyoDs). To date, there has not been a comprehensive, correlative categorization with respect to the fundamental anatomic/electrophysiologic origin and specific discharge characteristics for the above-noted waveforms. The underlying proposed basis for all ASMFGs is effectively an unstable resting membrane potential (RMP). This is predicated on specific combinations of ion channel dysfunctions that in turn generate unique stereotypical discharge patterns. The latter is consequent to ion channel disequilibrium, with each pathologic entity's waveform having specific types of ion channel gain- (GoF) or loss-of-function (LoF) characteristics. ASMFG producing FPs (IncrIA/CRDs as a subset of FP/PSWs) have both GoF skeletal muscle voltage-gated sodium (Na⁺)/potassium (K⁺) channels and LoF chloride (Cl^-) channels. Conversely, myotonic ASMFGs may have LoF Cl^-, or GoF Na⁺ voltage-gated channels, but normal functioning voltage-gated K⁺ channels. Such unique combinations of ion channel dysfunction directly result in the stereotypical discharge characteristics associated with each particular waveform: FPs and their derivatives being relatively slow and regular, while MyoDs are comparatively more rapid and variable in frequency. Therefore, all of the above-noted ASMFG are in effect channelopathies.