Ion channels & neurotransmitter receptors

1. Voltage gated channels

2. Ligand gated channels

2 types of channels on the membrane of nerve cells

Ionotropic receptors

Metabotropic receptors

2 types of receptor

Metabotropic receptors

• Membrane delimited

• Diffusible second messenger

Cyclic adenosine monophosphate (CAMP)

Diacyl glycerol DAG

Inositol triphosphate IP3

second messenger

HYPERPOLARIZATION

EFFLUX OF K, INFLUX OF CL-, CHANGE IN CELL MEMBRANE POTENTIAL

HYPERPOLARIZATION

Relaxation/resting potential on membrane

HYPERPOLARIZATION

Influx of anions

DEPOLARIZATION

INFLUX OF NA AND CA– CELL BECOMES + POSITIVE

DEPOLARIZATION

Influx of cations

DEPOLARIZATION

Contraction

REPOLARIZATION

CHANGE IN THE MEMBRANE POTENTIAL THAT RETURNS IT TO (-) NEGATIVE, HAPPENS AFTER DEPOLARIZATION

REPOLARIZATION

Restoration

Metabrotopic / G protein linked receptor

Type 2 receptor aka

Excitatory post-synaptic potential (EPSP)

Excitatory potential

depolarization (contraction)

Excitatory

Inhibitory post-synaptic potential (IPSP)

Inhibitory potential

Inhibitory

hyperpolarization (resting membrane)

Excitatory neurotransmitters

opens Na or Ca channels/ influx → depolarization (more positive) → nerve impulse

Norepinephrine, Dopamine, Acetylcholine, Glutamate, Aspartate

Excitatory neurotransmitters ex

Inhibitory neurotransmitters

opens Cl channels → hyperpolarization (more negative) → no nerve impulse

glycine, gamma-aminobutyric acid (GABA)

Inhibitory neurotransmitters ex

gamma-aminobutyric acid (GABA)

Major inhibitory neurotransmitter

Voltage gated channel

Respond to changes in membrane potential of the cell

Ligand gated channels

Bindings the ligands directly opens the channel

Tetrodotoxin (TTX)

Batrachotoxin (BTX)

A. Voltage-gated

A.1. Sodium channels

Tetrodotoxin (TTX)

Blocks channel from outside

Batrachotoxin (BTX)

Slows inactivation, shifts activation

Colombian frog

Batrachotoxin (BTX) sou

Puffer fish

Tetrodotoxin (TTX) source

Apamin

Charybdotoxin

A. Voltage-gated

A.2. Potassium Channels

Apamin

Blocks "small Ca-activated" K channel

Honeybee

Apamin source

Charybdotoxin

Blocks "big Ca-activated" K channel

Scorpion

Charybdotoxin source

Omega conotoxin (ω-CTX-GVIA)

Agatoxin (ω-AGA-IVA)

A.3 Calcium channels

Agatoxin (ω-AGA-IVA)

Blocks P-type channel

Funnel web spider

Agatoxin (ω-AGA-IVA) source

Omega conotoxin (ω-CTX-GVIA)

Blocks N-type channel

Pacific cone snail

Omega conotoxin (ω-CTX-GVIA) source

Nicotinic ACh receptor

GABAA receptor

Glycine receptor

AMPA receptor

B. Ligand-gated

α-Bungarotoxin

Nicotinic ACh receptor

Irreversible antagonist

α-Bungarotoxin mode of toxin

Marine snake

α-Bungarotoxin source

Picrotoxin

GABAA receptor

Blocks channel

Picrotoxin mode of toxin action

South Pacific plant

Picrotoxin source

Strychnine

Glycine receptor

Competitive antagonist

Glycine receptor mode of toxin

Indian plant

Glycine receptor source

Philanthotoxin

AMPA receptor

Blocks channel

AMPA receptor mode of toxin

Wasp

AMPA receptor source

Amphetamine Capsaicin

Sites of drug action

Release

Cocaine, TCA

Sites of drug action

Uptake

anticholinesterase

Sites of drug action

Degradation

Endocannabinoids

Sites of drug action

Receptor

Reserpine

Sites of drug action

Storage

More difficult for CNS

• Anatomic complexity

• Limitation of available techniques

Identification of central neurotransmitters

Localization

Biochemical analysis

Localization

Immunocytochemical (enzymes,peptides)

Release

Simulation of Brain slices

Release

Calcium dependency of release

Localization

Release

Synaptic mimicry

Criteria for neurotransmitter identification

Synaptic mimicry

Microiontophoresis

Synaptic mimicry

Physiological view

Synaptic mimicry

Pharmacological view