Biological Membranes - A. N. Ogurtsov 2012

Electrogenesis of Biomembranes
Mechanisms of Intercellular Signaling
Neuromuscular Junction

Acetylcholine acts as a neurotransmitter at the synapse between a motor neuron and a Muscle Cell, commonly referred to as the neuromuscular junction or neuromuscular synapse. A single motor neuron can form several hundred synapses with a single muscle cell.

The arrival of an Action Potential at the presynaptic terminal of the motor neuron opens Ca²⁺ channels (Figure 154(A)), and Calcium Ions trigger the exocytosis of acetylcholine.

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Figure 154 - Sequential activation of Ion Channels at the neuromuscular junction synapse: 1 - voltage-gated calcium channels; 2 - nicotinic Acetylcholine Receptor; 3 - voltage-gated sodium channel; 4 - sarcoplasmic reticulum Ca²⁺ channel

Sensitivity to acetylcholine is mediated by cholinergic receptors, which are broadly divided into two main types: muscarinic (found in smooth muscle and the Brain) and nicotinic (found in Skeletal Muscle and autonomic ganglia).

The nicotinic acetylcholine receptor expressed in muscle Cells is a Ligand-gated ion channel permeable to both Na⁺ and K⁺. In the open state, such a channel can conduct 15,000–30,000 Na⁺ or K⁺ ions per millisecond (or 15–30·10⁶ ions per second).

However, because the resting Membrane Potential of a muscle cell is close to the potassium equilibrium potential, the opening of the acetylcholine receptor channel produces virtually no net inward flux of potassium ions. Conversely, sodium ions flow into The Cell through this channel driven by both the electrical field (the cell Cytosol is negatively charged at rest) and the concentration gradient (Figure 154(B)).

The simultaneous increase in the permeability of the postsynaptic membrane to Na⁺ and K⁺ ions, resulting from the action of acetylcholine on the receptor, depolarizes the membrane by about -15 mV from its Resting Potential of approximately -90 mV. This local depolarization triggers the opening of voltage-gated Na⁺ channels (Figure 154(B)), which in turn induces the GENERATION AND PROPAGATION of an action potential across the muscle cell surface via the mechanism described above for Neurons.

When membrane depolarization reaches the T-tubules (specialized invaginations of The Plasma Membrane), the voltage-gated Ca²⁺ channels in this region undergo a conformational change. This in turn induces conformational shifts in the coupled ryanodine Ca²⁺ channels (Figure 141) located On the surface of the cell's sarcoplasmic reticulum (Figure 154(D)). This is followed by the release of Ca²⁺ ions from the sarcoplasmic reticulum into the cytosol, which triggers muscle cell contraction.