Why does sustained muscle contraction at high frequency ultimately lead to fatigue, despite ongoing neural stimulation?

💡 Explanation

Muscle fatigue during high-frequency stimulation arises from a progressive reduction in calcium release, causing reduced cross-bridge formation and force generation. This occurs because the sarcoplasmic reticulum's ability to sequester and release calcium is overwhelmed. Therefore, reduced calcium release causes fatigue, rather than other metabolic or ionic changes.

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