Content Reviewers:Rishi Desai, MD, MPH
Contributors:Evan Debevec-McKenney, Marisa Pedron, Antonella Melani, MD, Kara Lukasiewicz, PhD, MScBMC
Cholinergic receptors are receptors on the surface of cells that get activated when they bind a type of neurotransmitter called acetylcholine.
There are two types of cholinergic receptors, called nicotinic and muscarinic receptors - named after the drugs that work on them.
The nervous system is divided into the central nervous system, so the brain and spinal cord, and the peripheral nervous system, which includes all the nerves that connect the central nervous system to the muscles and organs.
The peripheral nervous system is divided into the somatic nervous system, which controls skeletal muscles, and the autonomic nervous system, which is further divided into the sympathetic and the parasympathetic, and controls internal organs.
Neurons are the main cells of the nervous system. They’re composed of a cell body, which contains all the organelles, and nerve fibers, which are projections that extend out from the neuron cell body.
Nerve fibers are dendrites that receive signals from other neurons, and axons that send signals along to other neurons.
Where two neurons come together is called a synapse; that’s where an axon releases neurotransmitters that bind to receptors present on the cell membrane of the dendrites or the cell body of the next neuron in the series.
Now the autonomic nervous system - so both sympathetic and parasympathetic - is made up of a relay that includes two neurons: preganglionic neurons, which have their cell bodies in nuclei throughout the spinal cord, and postganglionic neurons, which have their cells bodies in ganglia out of the spinal cord.
Axons of preganglionic neurons exit the spinal cord to reach the ganglia and synapse with postganglionic neurons. Then, the axons of postganglionic neurons exit the ganglia to reach the organs and synapse with the target organ cells.
Let’s zoom into the synapses. In the sympathetic nervous system, preganglionic and postganglionic neurons release different neurotransmitters.
Preganglionic neurons release the neurotransmitter acetylcholine, which binds to nicotinic receptors on the cell membrane of postganglionic neuron cell bodies.
A few sympathetic postganglionic neurons release acetylcholine, which binds to muscarinic receptors on target organ cells.
Now for the parasympathetic nervous system, both preganglionic and postganglionic neurons release acetylcholine.
The acetylcholine released by preganglionic neurons binds to nicotinic receptors on postganglionic neuron cell bodies.
Then, the postganglionic neurons release acetylcholine, but in this case it binds to the muscarinic receptors on the target organ cells.
Whenever a motor neuron receives an electrical impulse from the brain, this triggers the release of small vesicles that contain acetylcholine into the neuromuscular junction.
Acetylcholine then binds to the nicotinic receptors on skeletal muscle cells, and triggers skeletal muscle contraction.
Now, nicotinic receptors are also called ionotropic acetylcholine receptors, because they are ligand gated ion channels, which means that they open when acetylcholine binds, allowing positively charged ions like sodium and potassium to flow through them.
Nicotinic receptors are made of five subunits, two alpha, one beta, one gamma, and one delta subunit, and together they form a tunnel that’s generally closed.
When acetylcholine binds to the alpha subunits, the tunnel changes shape and opens up. That lets sodium flow into the cell, and potassium out of the cell, following a passive gradient. This leads to depolarization of the cell, which is when the cell undergoes a shift in electric charge distribution and becomes more positive, triggering a cellular response.
Muscarinic receptors are also known as metabotropic acetylcholine receptors because they activate intracellular proteins when acetylcholine binds.
Muscarinic receptors are seven pass transmembrane receptors, which means they are really long proteins that have one end that sits outside the cell and binds acetylcholine, then the snake-like protein dips in and out of the cell membrane seven times, and finally ends on the inside of the cell.
The end of the protein within the cell activates intracellular proteins.
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