Skeletal muscle is stimulated via a nerve impulse, which depolarises the muscle. However, not all the muscle fibres in the muscle fibre will necessarily be activated at once. Sometimes, a subset of muscle fibres is activated, depending on how much force is needed.

When the muscle is stimulated, calcium ions are released from its store inside the sarcoplasmic reticulum, into the sarcoplasm (muscle ).

Then the calcium ions bind to a protein called troponin, on the thin filaments, which in turn allows myosin to bind to actin. This interaction makes the thick and thin filaments slide past each other, to make the muscle shorten. (see Muscle Sarcomere)

Invaginations of the plasma membrane (sarcolemma) of the muscle fibres are called T (or transverse) tubules. The T-tubules lie over the junction between the A- and I-bands (see diagram).

The two terminal cistemae of the SR together with their associated T tubule are known as a triad.

Inside the muscle fibre, the T-tubules lie next to the terminal cisternae of an internal membrane system derived from the endoplasmic reticulum, called the sarcoplasmic reticulum (SR), which is a store of calcium ions. Stimulation of the muscle fibre, causes a wave of depolarisation to pass down the t-tubule, and the SR to release calcium ions into the sarcoplasm. Calcium is pumped back up into the SR to lower calcium ion concentration in the sarcoplasm, to relax the muscle (turn off contraction).

Cardiac Muscle also has T-tubules, and SR. However the T-tubules lie over the Z-line in cardiac muscle, are less numerous and wider. The SR is smaller and less elaborate, and stores less calcium ions. Cardiac muscle cells also depend on extracellular calcium ions, that enter through the T-tubules and triggers release of calcium ions from the SR.

Cardiac muscle cells are electrically connected through gap junctions, so that waves of electrical stimuli pass around the heart from cell to cell, and all the cells are stimulated to contract.

Smooth Muscle. The thick and thin filaments are attached to alpha-actinin in dense bodies (equivalent to Z-lines in skeletal muscle), which are attached to the plasma membrane by intermediate filaments. The thin filaments do not have troponin. This type of muscle responds to a increase in calcium, following nerve stimulation through a protein called calmodulin. Binding of calcium to calmodulin, results in the activation of an enzyme (myosin light chain kinase) that phosphorylates myosin, which activates it, enabling it to interact with actin.