Difference Between Nicotinic and Muscarinic Receptors

Main Difference – Nicotinic vs Muscarinic Receptors

Nicotinic and muscarinic receptors are the two main types of cholinergic receptors. They are integral membrane proteins activated by the binding of acetylcholine, a neurotransmitter. Though the same neurotransmitter binds to both types of receptors, the mechanism of action is different in each receptor. The main difference between nicotinic and muscarinic receptors is that nicotinic receptors become ion channels for sodium upon binding of the acetylcholine to the receptor whereas muscarinic receptors phosphorylate various second messengers. Nicotinic receptors are also called ionotropic acetylcholine receptors while muscarinic receptors are also called metabotropic acetylcholine receptors depending on their action.

Key Areas Covered

1. What are Nicotinic Receptors
– Definition, Facts, Mechanism of Action
2. What are Muscarinic Receptors
– Definition, Facts, Mechanism of Action
3. What are the Similarities Between Nicotinic and Muscarinic Receptors
– Outline of Common Features
4. What is the Difference Between Nicotinic and Muscarinic Receptors
– Comparison of Key Differences

Key Terms: Acetylcholine (Ach), Cholinergic Receptors, Ion Channels, Ionotropic Acetylcholine Receptors, Metabotropic Acetylcholine Receptors, Muscarinic Receptors, N1 Receptors, N2 Receptors, Nicotinic Receptors, Phosphorylation, Second Messenger

What are Nicotinic Receptors

Nicotinic receptors (nAhRs) are a group of cholinergic receptors that also interact with nicotine in tobacco. They form pores through the cell membrane of the post-ganglionic nerves. As nicotinic receptors serve as ligand-gated ion channels, they mediate the fast transmission of nerve impulses at synapses. The nicotinic receptors are permeable to cations such as sodium, potassium, and calcium. The formation of the ion channel upon the binding of the agonist results in the depolarization of the cell membrane of the neuron. This allows the fast transmission of the signal. The two types of nicotinic receptors are N1 and N2. The N1 receptors are muscle-type receptors found in the neuromuscular junctions. They are responsible for muscular contractions and relaxations. The N2 receptors are neuronal-type receptors found in the synapses between neurons. They are involved in cognitive function, memory, learning, arousal, reward, motor control, and analgesia. The structure of the nicotinic receptor is shown in figure 1.

Difference Between Nicotinic and Muscarinic Receptors

Figure 1: Nicotinic Receptor

The two types of nicotinic receptors are classified based on the types of subunits present in each nicotinic receptors. In vertebrates, they are composed of five subunits. In mammals, sixteen subunits can be identified in nicotinic receptors.

What are Muscarinic Receptors

Muscarinic receptors (mAChRs) are a group of cholinergic receptors that interact with muscarine. Muscarine is a water-soluble toxin derived from a mushroom (Amanita muscaria). The muscarinic receptors primarily occur in the central nervous system. They are a type of G-protein coupled receptors. Thus, upon activation of the muscarine receptor by the binding of the agonist, the intracellular G-proteins are activated, converting GTP to GDP. The M2 receptor structure is shown in figure 2.

Main Difference - Nicotinic vs Muscarinic Receptors

Figure 2: M2 Receptor

A large number of physiological functions such as heart rate and force, the release of neurotransmitters, and contraction of smooth muscles are mediated by muscarinic receptors. The five types of muscarinic receptors are M1, M2, M3, M4, and M5. They are categorized based on the physiological function. The M1 receptors commonly occur in secretory glands. The M2 is found in cardiac tissue, the M3 is found in both secretory glands and smooth muscles. The M1, M3, and M5 activate phospholipase C, increasing the intracellular calcium levels. The M2 and M4 inhibit adenylate cyclase, decreasing the cAMP levels.

Similarities Between Nicotinic and Muscarinic Receptors

Both nicotinic and muscarinic receptors are cholinergic receptors.
Both nicotinic and muscarinic receptors respond to the neurotransmitter, acetylcholine.
Both nicotinic and muscarinic receptors are found on the post-ganglionic neurons of both sympathetic and parasympathetic nervous systems.
Both nicotinic and muscarinic receptors undergo conformational changes upon binding the agonist.
Both nicotinic and muscarinic receptors respond to other molecules as well.

Definition

Nicotinic Receptors: Nicotinic receptors refer to a group of cholinergic receptors linked to ion channels in the cell membrane.

Muscarinic Receptors: Muscarinic receptors refer to a group of G-protein coupled cholinergic receptors that phosphorylate second messengers.

Types

Nicotinic Receptors: The two types of nicotinic receptors are N1 and N2.

Muscarinic Receptors: The five types of muscarinic receptors are M1, M2, M3, M4, and M5.

Excitatory/Inhibitory

Nicotinic Receptors: Nicotinic receptors are excitatory receptors.

Muscarinic Receptors: The M1, M2, and M5 are excitatory receptors while M3 and M4 are inhibitory receptors.

Occurrence

Nicotinic Receptors: The N1 receptors occur in the neuromuscular junctions. The N2 receptors occur in the brain, autonomic and parasympathetic nervous system.

Muscarinic Receptors: The muscarinic receptors occur in the brain, heart, and smooth muscles.

Mechanism of Action

Nicotinic Receptors: Nicotinic receptors become ion channels upon activation by acetylcholine.

Muscarinic Receptors: Muscarinic receptors phosphorylate various second messengers.

Called as

Nicotinic Receptors: Nicotinic receptors are called ionotropic acetylcholine receptors.

Muscarinic Receptors: Muscarinic receptors are called metabotropic acetylcholine receptors.

Type of Receptor

Nicotinic Receptors: Nicotinic receptors are a type of ligand-gated ion channels.

Muscarinic Receptors: Muscarinic receptors are a type of G-protein coupled receptors (GPCRs).

Role

Nicotinic Receptors: Nicotinic receptors mediate fast synaptic transmission of nerve impulses.

Muscarinic Receptors: Muscarinic receptors mediate a slow metabolic response via second messenger cascades.

Responsive to

Nicotinic Receptors: Nicotinic receptors also respond to nicotine.

Muscarinic Receptors: Muscarinic receptors also respond to muscarine.

Conclusion

Nicotinic and muscarinic receptors are the two main types of cholinergic receptors. Activated nicotinic receptors serve as ion channels while activated muscarinic receptors phosphorylate second messengers to mediate metabolic responses. The nicotinic receptors facilitate the transmission of nerve impulses. The main difference between nicotinic and muscarinic receptors is the mechanism of action of each type of receptors.

Reference:
1. Nicotinic acetylcholine receptors | Introduction | BPS/IUPHAR Guide to PHARMACOLOGY, Available here.
2. Acetylcholine receptors (Muscarinic) | Introduction | BPS/IUPHAR Guide to PHARMACOLOGY, Available here.

Image Courtesy:

1. “NAChR” By Ataly – Own work (CC BY-SA 3.0) via Commons Wikimedia
2. “Muscarinic acetylcholine receptor M2-3UON” By Takuma-sa – Own work (CC0) via Commons Wikimedia