title: An analysis of the relationships between subthreshold electrical properties and excitability in skeletal muscle.
abstract: Skeletal muscle activation requires action potential (AP) initiation followed by its sarcolemmal propagation and tubular excitation to trigger Ca(2+) release and contraction. Recent studies demonstrate that ion channels underlying the resting membrane conductance (G(M)) of fast-twitch mammalian muscle fibers are highly regulated during muscle activity. Thus, onset of activity reduces G(M), whereas prolonged activity can markedly elevate G(M). Although these observations implicate G(M) regulation in control of muscle excitability, classical theoretical studies in un-myelinated axons predict little influence of G(M) on membrane excitability. However, surface membrane morphologies differ markedly between un-myelinated axons and muscle fibers, predominantly because of the tubular (t)-system of muscle fibers. This study develops a linear circuit model of mammalian muscle fiber and uses this to assess the role of subthreshold electrical properties, including G(M) changes during muscle activity, for AP initiation, AP propagation, and t-system excitation. Experimental observations of frequency-dependent length constant and membrane-phase properties in fast-twitch rat fibers could only be replicated by models that included t-system luminal resistances. Having quantified these resistances, the resulting models showed enhanced conduction velocity of passive current flow also implicating elevated AP propagation velocity. Furthermore, the resistances filter passive currents such that higher frequency current components would determine sarcolemma AP conduction velocity, whereas lower frequency components excite t-system APs. Because G(M) modulation affects only the low-frequency membrane impedance, the G(M) changes in active muscle would predominantly affect neuromuscular transmission and low-frequency t-system excitation while exerting little influence on the high-frequency process of sarcolemmal AP propagation. This physiological role of G(M) regulation was increased by high Cl(-) permeability, as in muscle endplate regions, and by increased extracellular [K(+)], as observed in working muscle. Thus, reduced G(M) at the onset of exercise would enhance t-system excitation and neuromuscular transmission, whereas elevated G(M) after sustained activity would inhibit these processes and thereby accentuate muscle fatigue.
authors.affiliation: Physiological Laboratory, University of Cambridge, England, UK. thp@-fi.au.dk
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Pedersen
authors.forename: Christopher
authors.initials: C
authors.lastname: L-H Huang
authors.forename: James A
authors.initials: JA
authors.lastname: Fraser
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D005260:Female; D008564:Membrane Potentials / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000502:physiology