Neurotransmission utilizing acetylcholine is the signal used by all vertebrate motor nerve terminals to tell skeletal muscle to contract. Acetylcholine (ACh) activates its own specialized receptor in the muscle membrane and this leads to ionic flux between the inside and outside of a muscle cell. The resulting changes in muscle membrane voltage cause the opening of another specialized ion channel which propagates the nerve’s signal throughout the muscle membrane, activating still more ion channels, leading to contraction.
Skeletal muscle cells in all vertebrate species respond to the use of acetylcholine as the neurotransmitter by motor neurons. This is because they all have nicotinic acetylcholine receptors (nAChR) concentrated in their membrane across from the end of a motor nerve at the neuromuscular junction. The nAChR is a multiprotein complex consisting of 5 distinct interacting proteins that together form a channel through which ions can flow once the receptor has been activated.
All cells have a measurable voltage across their membrane, small to be sure, but measurable nonetheless. Changes in ion flow across the membrane, such as those caused by activation of the nAChR in muscle, lead to changes in this membrane voltage or potential. This is important in muscle that has been stimulated by nerve because it is this change, induced by ion flow through the nAChR, that leads to activation of another ion channel, the voltage-gated sodium channel. Once activated by the change in membrane voltage, it is these sodium channels that propagate the electrical stimulation of the muscle, otherwise known as the action potential.
When the action potential reaches specific structures in the muscle cell another set of ions are induced to move, calcium ions. The muscle cell normally stores calcium ions inside of specialized repositories inside of the cell. When they are stimulated by the changes in membrane potential, they activate their own ion channels, known as the ryanodine receptors, which lead to the release of calcium from these internal storehouses. The increase in calcium induces changes in the proteins that regulate contraction of muscle fibers allowing the, until that moment, relaxed actin and myosin complexes to begin sliding on each other and generating the force of muscle contraction.
At the end of a contraction, calcium ions are actively pumped away from the sliding filaments in the skeletal muscle cytoplasm back into their internal storage centers. This movement is accomplished through the action of another calcium ion channel, distinct from the one that released the calcium to begin with. Once the calcium has been sequestered, the contracting actomyosin complexes can relax.
Each of the ion channels described is important for normal skeletal muscle function. Without their activity, problems would clearly arise. In fact, several disorders are known to involve the channels that have been described above. For example, in many cases of myasthenia gravis, antibodies develop that target the acetylcholine receptors and this leads to muscle weakness. Or in the case of the disorder known as malignant hyperthermia, where those affected can have severe reactions to certain types of anesthesia, the problem is with the ryanodine receptor. All told, it is the control of ions and how they move across the muscle membrane that is important not only in good health, but also in some diseases.