The events already described (calcium entry, cross-bridge cycling) occur when a muscle fiber is excited to fire an action potential. An action potential is triggered in a muscle fiber when it is depolarized due to excitation at its synapse, the neuromuscular junction. Each muscle fiber has one neuromuscular junction, receiving input from just one somatic efferent neuron. An action potential in a somatic efferent neuron causes it to release the neurotransmitter acetylcholine (ACh). ACh binds to nicotinic receptors in a specialized region of the muscle fiber known as the motor endplate. ACh binding allows Na+ ions to enter the cell, causing a depolarizing excitatory postsynaptic potential (EPSP) that is above threshold and triggers an action potential.
The neuromuscular junction differs from typical synapses in the CNS in one critical way: the EPSP is always well above threshold. This means that under normal circumstances, an action potential in a somatic efferent neuron always elicits an action potential in the muscle fiber.
The figure shows a muscle cell EPSP in response to a single action potential in a somatic efferent neuron. Such a recording is made by blocking voltage-gated Na+ channels; this prevents the muscle action potential from occuring so that one sees just the EPSP. The dotted red line shows the threshold. The amount of ACh released with one neuronal action potential is enough to depolarize the muscle fiber well above the threshold for eliciting an action potential. The degree that the EPSP exceeds threshold is known as the safety factor.
In the autoimmune disorder myasthenia gravis, antibodies to the acetylcholine receptor reduce the number of functioning receptors at the motor endplate, decreasing the size of the EPSP and reducing the safety factor. Patients with this disorder have muscle weakness because somatic efferent neurons are less able to excite muscle cells.
Myasthenia gravis can be diagnosed using the electromyogram (EMG). The electromyogram is an extracellular recording of the electrical activity of motor units. A motor unit consists of a somatic efferent neuron and all the muscle fibers that it innervates. In the electromyogram, one records a potential known as the compound action potential, which is the summed action potentials of all the muscle fibers in the motor unit.
To diagnose myasthenia gravis, the compound action potential is measured in response to repetitive nerve stimulation. Repetitive stimulation of the nerve depletes ACh in the presynaptic terminal, causing a decrease in the amplitude of the EPSP. Normally, because of the high safety factor, EPSPs are still well above threshold to elicit an action potential. Therefore, repeated stimulation causes no change in the compound action potential because the somatic efferent neuron still excites every muscle fiber in the motor unit (left recording).
In myasthenia gravis, this slight decrease in ACh release can cause some EPSPs to fall below threshold, so some of the muscle fibers in the motor unit fail to fire action potentials. One sees a decline in the amplitude of the compound action potential with repeated stimulation (recording on the right) because fewer muscle fibers in the motor unit are firing action potentials.
Myasthenia gravis is treated with acetylcholinesterase inhibitors. The goal is to increase the amount of acetylcholine to promote excitation at the synapse.
Now, test your grasp of these concepts with the muscle quiz.
CALCIUM REGULATION OF CONTRACTION