Slide 6-Neurotransmitters

Shortcut Pathway

from receptor to G-protein to ion channel-fast and localized

second messenger cascade pathway

process that couples the neurotransmitter via multiple steps to activation of a downstream enzyme

G-protein

couples neurotransmitters with downstream enzyme activation

Gi

adenylyl cyclase inhibitory Ga protein

Gs

adenylyl cyclase stimulatory Ga protein

Divergence

one transmitter activates more than one receptor subtype and has greater postsynaptic response

Convergence

different transmitters converge to affect same effector system

Integrative Divergence and Convergence

Describes how multiple signals can either activate various pathways (divergence) or how different signals can influence a single pathway (convergence) in G-protein signaling.

• 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