Related Experiment Video
Updated: Jun 19, 2026
A Preclinical Model of Sepsis-Induced Myopathy with Disuse in Mice
Published on: June 14, 2024
Enhanced muscle shortening and impaired Ca2+ channel function in an acute septic myopathy model
Oliver Friedrich1, Ernst Hund, Frederic von Wegner
1Medical Biophysics, Department of Systems Physiology, Institute of Physiology and Pathophysiology, University of Heidelberg, INF 326, 69120, Heidelberg, Germany. oliver.friedrich@physiologie.uni-heidelberg.de
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.
Insights
Serum from critical illness myopathy patients acutely impairs L-type Ca(2+) channel function in skeletal muscle fibers. Unexpectedly, this serum also slightly increases muscle fiber shortening speed, suggesting a potential early diagnostic marker.
Area of Science:
- Physiology
- Pathophysiology
- Biophysics
Background:
- Myopathies in critically ill patients are common but immediate changes during acute sepsis are poorly understood.
- Existing animal models focus on chronic sepsis, neglecting acute effects on skeletal muscle excitability and contractility.
- L-type Ca(2+) channel function and isotonic shortening dynamics during acute sepsis remain under-characterized.
Purpose of the Study:
- To investigate the acute effects of critical illness myopathy (CIM) patient serum on L-type Ca(2+) currents (I(Ca)) and isotonic shortening in mouse skeletal muscle fibers.
- To characterize immediate changes in skeletal muscle function during acute sepsis relevant to myopathy.
- To explore potential early diagnostic features of CIM.
Main Methods:
- Recorded L-type Ca(2+) currents (I(Ca)) in voltage-clamped single intact mouse skeletal muscle fibers.
- Applied serum fractions from CIM patients to assess acute effects.
- Simultaneously recorded unloaded fiber shortening using high-speed imaging (approx. 1,600 frames/s).
- Analyzed fiber length and shortening velocity using automated imaging algorithms.
Main Results:
- CIM serum fractions acutely reduced I(Ca) amplitudes without altering I(Ca)-V relations or voltage-dependent inactivation.
- I(Ca) activation and inactivation kinetics were prolonged by CIM serum.
- Maximum unloaded speed of shortening unexpectedly increased slightly after CIM serum application.
- Results suggest CIM serum may acutely reduce functional L-type Ca(2+) channels and affect cross-bridge dynamics.
Conclusions:
- CIM serum acutely depresses L-type Ca(2+) channel function and alters cross-bridge kinetics in skeletal muscle.
- These findings may explain reduced SR Ca(2+) release and force production in CIM patients.
- Increased isotonic shortening velocity could serve as an early diagnostic feature for CIM.
- The acute challenge model effectively bypasses chronic sepsis-related confounding factors like atrophy.
Related Concept Videos
01:29Relaxation of Skeletal Muscles
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated sodium channels. Sodium ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated calcium channels to open.
01:26Chemical Synapses
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
01:26Chemical Synapses
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
01:11Alterations in Muscle Tone lll
01:29Tetanus
01:26Cross-bridge Cycle