Critical illness myopathy serum fractions affect membrane excitability and intracellular calcium release in mammalian skeletal muscle.
The pathogenesis of myopathies occurring in critically ill patients (critical illness myopathy, CIM) is poorly understood. Both local and systemic responses to sepsis and other severe insults to the body are presumed to be involved but the precise mechanisms by which muscle function is impaired are far from clear. To elucidate such mechanisms we investigated the effects of blood serum fractions (5 kDa to 100 kDa molecular weight cut-off, MWCO) from patients with CIM and from control persons on membrane and contractile functions in intact mammalian single skeletal muscle fibres and chemically skinned fibre bundles. In intact fibres, resting membrane potentials were less negative when exposed to CIM serum fractions compared with control serum fractions. Half-width and maximum rise time of action potentials (AP) were smaller in CIM serum low MWCO fractions vs. control serum. Peak amplitudes of fast inward sodium currents (I(Na)) were increased by low MWCO-CIM fractions compared with control sera fractions. Additionally, voltage dependent inactivation of I(Na) was shifted towards more positive potentials by high MWCO fractions of CIM sera. In skinned fibres, pCa-force relations were similar in CIM and control serum fractions but peak force of Ca2+ induced force transients was decreased by low MWCO-CIM vs. control serum fractions. Our results (i) provide the first evidence that serum from CIM patients affects membrane excitability and the excitation-contraction coupling process at the level of the sarcoplasmic reticulum Ca2+ release of mammalian muscle fibres and (ii) also show that even control serum fractions "per se" alter the response to important physiological membrane and contractility parameters compared with physiological saline.
Medical Biophysics Institute of Physiology & Pathophysiology, Ruprecht-Karls-University, Im Neuenheimer Feld 326, Heidelberg, Germany.
Oliver
O
Friedrich
Ernst
E
Hund
Cornelia
C
Weber
Werner
W
Hacke
Rainer H A
RH
Fink
D000818:Animals; D001798:Blood Proteins / Q000145:classification / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D016022:Case-Control Studies; D020552:Comet Assay / Q000379:methods; D016638:Critical Illness; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects*; D009135:Muscular Diseases / Q000097:blood*; D018408:Patch-Clamp Techniques / Q000379:methods; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D044967:Serum / Q000737:chemistry*; D015222:Sodium Channels / Q000187:drug effects; D013997:Time Factors
D001798:Blood Proteins; D015222:Sodium Channels; D002118:Calcium