Spontaneous activity in denervated mouse diaphragm muscle

Area of Science:

• Neuroscience
• Muscle Physiology
• Cellular Electrophysiology

Background:

• Chronic denervation of skeletal muscles leads to spontaneous electrical activity.
• This activity, characterized by discrete depolarizations, is implicated in the generation of fibrillation potentials.

Purpose of the Study:

• To investigate the underlying mechanisms of spontaneous depolarizations in denervated mouse diaphragm muscles.
• To identify factors influencing the generation and modulation of this activity.

Main Methods:

• Intracellular recordings from chronically denervated mouse diaphragm muscle fibers in vitro.
• Manipulation of extracellular calcium concentration, application of tetrodotoxin, catecholamines (isoprenaline, adrenaline), and ouabain.
• Muscle fiber detubulation using glycerol or hypertonic solutions.

Main Results:

• Spontaneous activity emerged 3-12 days post-denervation, localized to the muscle center.
• Activity was dependent on external calcium, blocked by tetrodotoxin, and enhanced by catecholamines and ouabain.
• Detubulation abolished activity, suggesting a role for the transverse tubular system.

Conclusions:

• Spontaneous depolarizations in denervated muscle fibers arise from regenerative sodium conductance increases within the transverse tubular system.
• Catecholamines and ouabain modulate this activity, potentially via direct effects on membrane excitability or indirectly through the Na+-K+ pump.