Ca2+-dependent slow action potentials in normal and dystrophic mouse skeletal muscle

Area of Science:

• Muscle Physiology
• Neuroscience
• Biophysics

Background:

• Slowly rising action potentials (APs) were previously observed in amphibian skeletal muscle.
• These slow APs are distinct from the fast sodium channel-dependent APs typical of mammalian skeletal muscle.

Purpose of the Study:

• To investigate the characteristics of slow APs in mammalian skeletal muscle.
• To compare slow APs in normal and dystrophic mouse skeletal muscle.
• To elucidate the ionic mechanisms underlying slow APs and their potential role in muscular dystrophy.

Main Methods:

• Two-microelectrode recording technique in isolated mouse skeletal muscle fibers.
• Experimental conditions included a chloride-free, high potassium (20 mM) solution with tetraethylammonium.
• Slow APs were elicited under conditions of fast sodium channel inactivation and low external sodium (10 mM), with varying external calcium concentrations and calcium channel blockers.

Main Results:

• Slow APs were successfully elicited in mammalian skeletal muscle and were dependent on extracellular calcium.
• Increases in external calcium enhanced slow AP amplitude and duration; calcium antagonists and specific ions (Mn2+, La3+) blocked these APs.
• Dystrophic muscle fibers exhibited significantly reduced slow AP amplitude, duration, and occurrence compared to normal fibers.

Conclusions:

• Slow calcium-dependent action potentials (APs) occur in mammalian skeletal muscle, similar to cardiac and amphibian muscle.
• These slow APs are depressed in dystrophic mouse skeletal muscle, suggesting a potential contribution of altered calcium handling to the disease.
• The findings highlight the importance of calcium channels in mammalian skeletal muscle excitability and their potential dysfunction in muscular dystrophy.