Neurotransmitters and their transporters

• Vesicular GABA transporter (vGAT)

• Vesicular glutamate transporter (vGlut)

What specific transporters are required for GABA and Glutamate to load into the synaptic vesicles?

Agonists

are substances that bind to receptors and activate them, mimicking the action of neurotransmitters.

Antagonists

are substances that bind to receptors but block or inhibit their function, preventing neurotransmitters from exerting their effects.

nicotinic & muscarinic

ACh receptors

AMPA, NMDA, and kainate

3 subtypes of Glutamate receptors

Glutamate receptors

activates all three receptor subtypes, but AMPA receptor only acts with the AMPA receptor

tetramer

having four subunits that comprise a functional channel which form a pore

pentamer

five protein subunits arranged like the staves of a barrel to form a single pore through the membrane

Glutamate-gated channels

the receptors of this channel resembles that of some potassium channels

• AMPA, NMDA, kainate receptors

• AMPA receptors permeable to Na+ and K+

• NMDA receptors permeable to Na+ and K+ and Ca2+

Amino Acid Gated Channels - NMDA

Voltage-dependent NMDA channels however blocked by Mg2+ ions at negative resting membrane potentials. Removal of Mg2+ block accomplished by membrane depolarization

• require glutamate binding AND membrane depolarization to open channel

Amino Acid Gated Channels - GABA_A

GABA-gated and glycine-gated channels which GABA mediates most synaptic inhibition in CNS while Glycine mediates non-GABA synaptic inhibition

• bind ethanol, benzodiazepines, barbiturates

Endocannabinoids

can be released from post-synaptic neurons and act on presynaptic terminals, which makes them retrograde messengers. They act on presynaptic G-protein coupled receptor and cannabinoid receptors

G-protein coupled receptors

single polypeptide with seven membrane spanning alpha helices, membrane protein activates G-proteins when it binds neurotransmitter

• binding of neurotransmitter to receptor protein

• activation of G-proteins

• activation of effector systems

3 Steps signaling by G-protein coupled receptors