Question

Describe the structure of nicotinic ACh receptors, and how ACh interacts with these receptors to cause the production of an EPSP.

Short answer

Nicotinic ACh receptors consist of five symmetrically arranged subunits forming a central pore. The most common form includes two α1, one β1, one γ (or ε), and one δ subunit. When acetylcholine (ACh) is released into the synaptic cleft, it binds to the receptor's extracellular domain. Each receptor has two ACh-binding sites located at the interface between the α and non-α subunits. The binding of ACh leads to a conformational change in the receptor's structure, resulting in the opening of central pore, which allows the flow of Na+ and K+ ions. This net influx of positive ions depolarizes the postsynaptic cell membrane, generating an excitatory postsynaptic potential (EPSP), which helps propagate the neural signal.

Step-by-step solution

Introduction to Nicotinic ACh Receptors

Nicotinic acetylcholine (ACh) receptors are a type of ligand-gated ion channel found in the central and peripheral nervous systems. They are activated by the binding of the neurotransmitter acetylcholine, which initiates an excitatory response in the postsynaptic cell. The structure of these receptors is essential for understanding their function and how they contribute to the generation of an EPSP.

Structure of Nicotinic ACh Receptors

Nicotinic ACh receptors are composed of five subunits arranged symmetrically around a central pore. These subunits can be different in their composition, including combinations of α, β, γ, and δ subunits, but the most common form found in the neuromuscular junction is the combination of two α1, one β1, one γ (or ε), and one δ subunit. The receptor has an extracellular domain, where ACh binds, a transmembrane domain that forms the ion channel, and an intracellular domain that interacts with other proteins and the cell cytoskeleton.

Binding of Acetylcholine to the Receptor

When acetylcholine is released into the synaptic cleft, it diffuses in the extracellular space and binds to the extracellular domain of the nicotinic ACh receptor. Each receptor has two ACh-binding sites, which are located at the interface between the α and one of the non-α subunits. The binding of ACh is a reversible process and involves interactions with specific amino acid residues in the receptor's binding pocket.

Conformational Change and Ion Channel Opening

The binding of ACh to the receptor leads to a conformational change in the receptor's structure. This change causes the central pore of the receptor to open, allowing the flow of ions through the channel. Nicotinic ACh receptors are primarily permeable to Na+ ions (sodium) which flow into the cell, and K+ ions (potassium) which flow out of the cell on the postsynaptic cell membrane.

Generation of an Excitatory Postsynaptic Potential (EPSP)

As a result of the ion flow through the open channel, there is an influx of positively charged Na+ ions and a smaller efflux of K+ ions. The net effect is a depolarization of the postsynaptic cell membrane, which means there is an increased likelihood of the postsynaptic neuron reaching its threshold and generating an action potential. This change in membrane potential is called an excitatory postsynaptic potential (EPSP). The EPSP helps to propagate the signal from the presynaptic neuron to the postsynaptic neuron and, ultimately, through the neural circuit.