The nucleotide receptors on mouse C2C12 myotubes

Area of Science:

• Cellular electrophysiology
• Molecular pharmacology
• Muscle physiology

Background:

• C2C12 mouse myotubes are a widely used model for studying muscle cell function.
• Nucleotides, such as adenosine triphosphate (ATP) and uridine triphosphate (UTP), are known signaling molecules in various cell types.
• The specific mechanisms by which nucleotides influence myotube membrane potential are not fully elucidated.

Purpose of the Study:

• To investigate the effects of adenosine triphosphate (ATP) and other nucleotides on the membrane potential of C2C12 mouse myotubes.
• To characterize the ionic mechanisms underlying nucleotide-induced membrane potential changes.
• To identify potential nucleotide receptors involved in these responses.

Main Methods:

• Measurement of changes in membrane potential of C2C12 myotubes upon stimulation with various nucleotides.
• Experiments conducted under different ionic conditions (e.g., calcium-free, low sodium).
• Application of specific channel blockers and antagonists (e.g., tetraethylammonium, apamin, suramin).

Main Results:

• ATP induced a transient hyperpolarization followed by a sustained depolarization, dependent on extracellular calcium and involving potassium and sodium conductances.
• ATP gamma S and UTP also elicited hyperpolarization, blocked by apamin and calcium removal, suggesting involvement of calcium-activated potassium channels.
• UTP-induced depolarization was sodium-dependent and distinct from ATP's effects, with suramin showing competitive antagonism, indicating separate receptor-mediated pathways.

Conclusions:

• C2C12 myotubes possess distinct nucleotide receptors that mediate differential responses to ATP and UTP.
• ATP-induced responses involve both calcium-dependent potassium currents and sodium currents.
• UTP-induced responses are primarily mediated by a distinct pathway, highlighting the complexity of purinergic signaling in muscle cells.