Types of receptors

Peptides

Large molecules (chains of amino acids)

Act on metabotropic receptors
Slower, longer lasting, and more modulatory effects compared with classical NT
Often coexist in the same axon terminals with other amine or amino acid NT. They are stored in seperate vesicles and released under different conditions

Oxytocin

Social bonding, trust and maternal behaviour
Regulates stress
As a hormone: Stimulates uterine contractions during labor and lactation during breastfeeding

Gasotransmitters

Molecules of soluble gas that dissolve into watery cellular environment during synthetization
Involved in synaptic plasticity and learning, regulates blood flow

Gasotransmitter production

In locations other than axons (especially dendrites)
Not held in vesicles
No interaction with membrane-bound receptors; diffuses out and into cells

Retrograde transmitter
part of gasotransmitters

diffuses from postsynaptic neuron back to the presynaptic neuron

Receptors

Protein molecules embedded in postsynaptic membrane that recognize a specific NT
Ionotropic and Metabotropic

Ionotropic (ligand-gated)

NT causes an ion channel to open

Metabotropic (G-protein coupled)

NT activates chemical reactions within the target cell. May involve a second messenger

Ionotropic Receptor structure

four or five subunits together forming a pore
pore is usually closed in the absence of NT
NT binds to specific site(s)
Opening of channel induces a post-synaptic potential

Ionotropic blinding

Causes a slight twist of subunits, opening the pore within microseconds

Nicotonic Acetylcholine (ACh) Receptor

Each receptor consists of five subunits
Receptor’s two ligand-binding sites preferentially bind acetylcholine, but they can also bind exogenous agonists such as nicotine and other nicotinic compounds

Properties of ionotropic receptors

Most ligand-gated channels are medicated by amino acid NTs (Glutamate, GABA, glycine), some are not amino acid based (eg, nicotinic ACh, one for serotonin)

Ionotropic receptors - pharmacology

describes which NT affect them and how drugs interact with them

ionotropic receptors kinetics

NT binding process- channel gating determine duration of their effect

ionotropic receptors selectivity

Ion channels determine whether they produce excitation or inhibition

Ion entry into ligand-gated channels

transmitter gated channels generally do not show the same degree of ion selectivity as voltage-gated channels

Nicotinic ACh-gated channels at the neuromuscular junction

Permeable to Na and K
If open channels are permeable to Na, the net effect is depolarization of the postsynaptic cell

EPSP

Resulting change in membrane potential (Vm), as recorded by a microelectrode in the cell is the EPSP
Na entering postysynaptic cell causes membrane depolarization

Inhibitory Postsynaptic Potential (IPSP)

Cl entering postsynaptic cell causes membrane hyperpolarization
Resulting change in membrane potential (Vm), as recorded by a microelectode in the cell is the IPSP

Metabotropic Receptors

Lower, longer lasting, and more diverse postsynaptic actions

Metabotropic Receptors Steps

1. NT binds to receptor proteins embedded in the postsynaptic membrane

2. Receptor protein activate small proteins, called G-proteins, which move along the intracellular face of the postsynaptic membrane

3. Activated G-proteins split into subunits (alpha and beta-gamma)

4. Target “effector” proteins. May be ion channels or enzymes that generate intracellular second messengers

Receptor Complexity

Each NT can act on multiple receptor subtypes with different anatomical distributions and effects
Effects determined by the receptor
Allows divergence and convergence of signals

Convergence

• Multiple NTs, each binding to their own receptor type, can influence the same effector system

• In a single cell, convergence can occur at the level of G-proteins, second messenger cascades, or ion channels

Divergence

• A single neurotransmitter (NT) can activate multiple receptor subtypes, producing different postsynaptic responses.

• One NT can affect different neurons (or even different parts of the same neuron) in distinct ways

• Can occur beyond the receptor, depending on the G-proteins and effector systems involved, at any stage of the signaling cascade

Key Concept

Effect is determined by the receptor, not by the NT

Different receptor subtypes

May trigger different responses in target cells
Same NT affects various kinds of receptors
Distribution of receptor subtypes varies across the nervous system