Enhanced muscle shortening and impaired Ca2+ channel function in an acute septic myopathy model.

Friedrich O, Hund E, von Wegner F (2010)

Publication Language: English

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2010

Journal

Journal of Neurology Springer Verlag (Germany)

Book Volume: 257

Pages Range: 546-55

Journal Issue: 4

URI: http://link.springer.com/article/10.1007%2Fs00415-009-5362-5

DOI: 10.1007/s00415-009-5362-5

Abstract

Myopathies in critically ill patients are increasingly documented. Various animal models of chronic sepsis have been employed to investigate reduced membrane excitability or altered isometric contractility of skeletal muscle. In contrast, immediate changes occurring during acute sepsis are significantly under-characterised; L-type Ca(2+) channel function or isotonic shortening are examples. We recorded slowly activating L-type Ca(2+) currents (I (Ca)) in voltage-clamped single intact mouse skeletal muscle fibres and tested the effects of acute challenge with serum fractions from critical illness myopathy patients (CIM). Using a high-speed camera system, we simultaneously recorded unloaded fibre shortening during isotonic contractions with unprecedented temporal resolution (approximately 1,600 frames/s). Time courses of fibre lengths and shortening velocity were determined from automated imaging algorithms. CIM fractions acutely induced depression of I (Ca) amplitudes with no shifts in I (Ca)-V-relations. Voltage-dependent inactivation was unaltered and I (Ca) activation and inactivation kinetics were prolonged compared to controls. Unexpectedly, maximum unloaded speed of shortening was slightly faster following CIM serum applications, suggesting a direct action of CIM serum on weak-binding-state cross-bridges. Our results are compatible with a model where CIM serum might acutely reduce a fraction of functional L-type Ca(2+) channels and could account for reduced SR Ca(2+) release and force production in CIM patients. Acute increase in isotonic shortening velocity might be an early diagnostic feature suitable for testing in clinical studies. The acute challenge model is also robust against atrophy or fibre type changes that ordinarily would have to be considered in chronic sepsis models.

Authors with CRIS profile

Oliver Friedrich Lehrstuhl für Medizinische Biotechnologie

Related research project(s)

Membrane Excitability and Cellular Calcium Regulation in the peripheral Nervous System under different (patho)-physiological Conditions and in Inflammatory Disease (ARC International Linkage Fellowship) April 1, 2008 - March 31, 2009

Involved external institutions

Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Goethe-Universität Frankfurt am Main DE Germany (DE)

How to cite

APA:

Friedrich, O., Hund, E., & von Wegner, F. (2010). Enhanced muscle shortening and impaired Ca2+ channel function in an acute septic myopathy model. Journal of Neurology, 257(4), 546-55. https://doi.org/10.1007/s00415-009-5362-5

MLA:

Friedrich, Oliver, Ernst Hund, and Frederic von Wegner. "Enhanced muscle shortening and impaired Ca2+ channel function in an acute septic myopathy model." Journal of Neurology 257.4 (2010): 546-55.

BibTeX: Download