# 10.5J: Ionotropic and Metabotropic Receptors


Although both ionotropic and metabotropic receptors are activated by neurotransmitters, ionotropic receptors are channel-linked while metabotropic receptors initiate a cascade of molecules via G-proteins.

##### Learning Objectives
• Distinguish between ionotropic and metabotropic receptors

## Key Points

• Two types of membrane bound receptors (ionotropic and metabotropic) are activated with the binding of neurotransmitters.
• Ionotropic receptors such as nicotinic acetylcholine are a group of transmembrane ion channels that open or close in response to the binding of a chemical messenger.
• Metabotropic receptor are a type of G protein -coupled receptor
• When a metabotropic receptor is activated, a series of intracellular events are triggered that can also result in ion channels opening but must involve a range of second messenger chemicals.

## Key Terms

• nicotinic acetylcholine receptor: A pentamer of protein subunits with two binding sites for acetylcholine which, when bound, alter the receptor’s configuration and cause an internal pore to open.
• Ionotropic receptors: A group of transmembrane ion channels that open or close in response to the binding of a chemical messenger (ligand) such as a neurotransmitter.
• metabotropic receptors: A subtype of membrane receptors that do not form an ion channel pore but use signal transduction mechanisms, often G proteins, to activate a series of intracellular events using second messenger chemicals.

Two types of membrane-bound receptors are activated with the binding of neurotransmitters: ligand-gated ion channels (LGICs) inotropic receptors and metabotropic G- protein coupled receptors.

## Ionotropic Receptors

Ionotropic receptors are a group of transmembrane ion channels that open or close in response to the binding of a chemical messenger (ligand) such as a neurotransmitter.The binding site of endogenous ligands on LGICs protein complexes are normally located on a different portion of the protein (an allosteric binding site) than the location of the ion conduction pore.The ion channel is regulated by a ligand and is usually very selective to one or more ions such as Na+, K+, Ca2+, or Cl.

The prototypic ligand-gated ion channel is the nicotinic acetylcholine receptor. It consists of a pentamer of protein subunits with two binding sites for acetylcholine which, when bound, alter the receptor’s configuration and cause an internal pore to open. This pore allows Na+ ions to flow down their electrochemical gradient into the cell. With a sufficient number of channels opening at once, the inward flow of positive charges carried by Na+ ions depolarizes the postsynaptic membrane enough to initiate an action potential.

## Metabotropic Receptors

Metabotropic receptors are a subtype of membrane receptors that do not form an ion channel pore but use signal transduction mechanisms, often G proteins, to activate a series of intracellular events using second messenger chemicals. Examples of metabotropic receptors include glutamate receptors, muscarinic acetylcholine receptors, GABAB receptors, most serotonin receptors, and receptors for norepinephrine, epinephrine, histamine, dopamine, neuropeptides, and endocannabinoids.

The metabotropic G protein-coupled receptors have seven hydrophobic transmembrane domains. When the neurotransmitter binds to the receptor, there is an activation via the G-protein that later activates the secondary messengers. Metabotropic receptors on the presynaptic membrane can inhibit or more rarely facilitate neurotransmitter release from the presynaptic neuron.

Since opening channels by metabotropic receptors involves activating a number of molecules in the intracellular mechanism, these receptors take longer to open than the inotropic receptors. They have a much longer effect than ionotropic receptors, which open quickly but only remain open for a few milliseconds. While ionotropic channels have an effect only in the immediate region of the receptor, the effects of metabotropic receptors can be more widespread throughout the cell.

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