1. In skeletal muscle, excitation-contraction (E-C) coupling describes a cascade of cellular events initiated by an action potential (AP) at the surface membrane that ultimately results in muscle contraction. Being able to specifically manipulate the many processes that constitute E-C coupling, as well as the many factors that modulate these processes, has proven challenging. 2. One of the simplest methods of gaining access to the intracellular environment of the muscle fibre is to physically remove (mechanically skin) the surface membrane. In doing so, the myoplasmic environment is opened to external manipulation. 3. Surprisingly, even though the surface membrane is absent, it is still possible to activate both twitch and tetanic force responses in a mechanically skinned muscle fibre by generating an AP in the transverse tubular system. This proves that all the key steps in E-C coupling are retained in this preparation. 4. By using this technique, it is now possible to easily manipulate the myoplasmic environment and observe how altering individual factors affects the normal E-C coupling sequence. The effect of important factors, such as the redox state of the cell, parvalbumin and the sarcoplasmic reticulum Ca2+-ATPase, on twitch and tetanic force can now be specifically investigated independent of other factors.
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