Postsynaptic Receptors: Ionotropic vs. Metabotropic in Neurotransmission

Ionotropic Receptors

Large protein complex, multiple subunits forming a channel.

Metabotropic Receptors

Single polypeptide with 7 transmembrane domains, interacts with G-proteins.

Nicotinic ACh

Ionotropic receptor located at the neuromuscular junction, providing a fast excitatory response with Na⁺ and K⁺ ions.

Muscarinic ACh

Metabotropic receptor located in smooth/cardiac muscle, providing a slow modulatory response mediated by G-proteins.

AMPA (Glutamate)

Ionotropic receptor in the CNS that mediates fast excitatory responses through Na⁺ influx.

NMDA (Glutamate)

Ionotropic receptor in the CNS that mediates slow responses with Ca²⁺ influx, requiring depolarization and Mg²⁺ removal.

Kainate (Glutamate)

Ionotropic receptor in the CNS that mediates fast excitatory responses through Na⁺/K⁺.

GABA-A

Ionotropic receptor in the CNS that mediates fast inhibitory responses through Cl⁻ influx, leading to hyperpolarization.

GABA-B

Metabotropic receptor in the CNS that mediates slow inhibitory responses by opening K⁺ channels and inhibiting Ca²⁺ channels.

Resting Potential

Condition where channel opens and ions move depending on the driving force.

Equilibrium Potential

State where there is no net movement of ions, even if channels are open.

EPSP (Excitatory Postsynaptic Potential)

Occurs when ion reversal potential is more positive than action potential threshold, leading to depolarization of the neuron.

IPSP (Inhibitory Postsynaptic Potential)

Occurs when ion reversal potential is more negative than action potential threshold, leading to hyperpolarization of the neuron.

Acetylcholinesterase

Enzyme that breaks down ACh in the synaptic cleft, stopping neurotransmission.

Reuptake Transporters

Proteins that remove neurotransmitters intact from the synaptic cleft for recycling or degradation inside presynaptic neurons or glial cells.

NMDA Receptors

Receptors that act as coincidence detectors, only opening when presynaptic activity and postsynaptic depolarization occur together.

Ca²⁺ Permeability

Property of NMDA receptors that triggers plasticity pathways.

Mg²⁺ Block

Condition at resting potential in NMDA receptors that is removed by depolarization.

Coincidence Detection

Mechanism in NMDA receptors that requires glutamate, a co-agonist, and depolarization to open.

Driving Force

The force that determines the movement of ions based on their concentration gradient and membrane potential.

Hyperpolarization

An increase in the membrane potential of a cell, making it more negative.

Depolarization

A decrease in the membrane potential of a cell, making it less negative.

SSRIs

Block serotonin reuptake transporter (SERT) → increases serotonin in synaptic cleft

THC (Tetrahydrocannabinol)

Mimics endocannabinoids (anandamide) → binds CB1 receptors

cAMP Second Messenger System

Neurotransmitter binds metabotropic receptor (GPCR)

Protein Kinases

Adds phosphate → activates proteins

Phosphatases

Removes phosphate → deactivates proteins

Facilitation

Residual Ca²⁺ enhances NT release → Enhances signal transmission

Synaptic depression

NT depletion reduces release → Prevents overstimulation

Augmentation

Increased NT release over seconds → Temporary strengthening

Post-tetanic potentiation

Elevated Ca²⁺ after tetanus → stronger release → Supports short-term memory

Short-term sensitization

Minutes → temporary behavioral changes

Long-term sensitization

Hours to days → structural and transcriptional changes

Long-Term Potentiation (LTP)

Long-lasting increase in synaptic strength

Early LTP (E-LTP)

Ca²⁺ influx via NMDA receptors → activates kinases → phosphorylates AMPA receptors

Late LTP (L-LTP)

Requires gene transcription & protein synthesis → new receptors, structural changes

Long-Term Depression (LTD)

Long-lasting decrease in synaptic strength

Cell signaling molecule

Extracellular molecule that triggers intracellular response → Neurotransmitter (glutamate, dopamine)

Receptor

Protein that binds signaling molecule → NMDA receptor, GPCR

Second messenger

Intracellular molecule that propagates signal → cAMP, IP₃, DAG

Heterotrimeric G-protein

G-protein with α, β, γ subunits activated by GPCR → Gs activating adenylyl cyclase

Transcription factor

Protein regulating gene expression → CREB phosphorylated by PKA