BIOL 3300 - Chapter 6 Notes

5 criteria for a neurotransmitter

1. synthesis and storage in presynaptic neuron

2. released by presynaptic axon terminal

3. when applied, mimics postsynaptic cell response produced by release of neurotransmitter from the presynaptic neuron

4. must be removed from the synapse

5. binds to specific receptor

G-protein coupled effector systems

three steps in transmission

• binding of the neurotransmitter to the receptor protein

• activation of G proteins

• activation of effector systems

the shortcut pathway

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

second messenger cascades

• G protein: couples neurotransmitter with downstream enzyme activation

• secondary messengers - cAMP and cGMP

push-pull method - different G proteins stimulate or inhibit adenylyl cyclase

signal amplification

Cholinergic receptors and subtypes

neuropharmacological analysis

• agonist - binds to a receptor and activates it

• antagonist - inhibits or prevents the activity of the receptors

• ACh receptors

  • nicotinic

    • ligand-gated ion channels (Na+, K+, Ca2+)

    • subtypes Nm/N1 found on muscle

    • subtypes Nn/N2 found on neurons

  • muscarinic

    • receptors g-protein

Glutamate and noradrenergic receptors

Glutamate ionotropic receptors

• AMPA

• NMDA

  • Glutamate must bind to it

  • Mg+ is bound to the opening, so another neurotransmitter must bind to a nearby receptor to raise the membrane potential

  • coincidence detector

• Kainate

Glutamate G protein receptors

• 3 types:

  • group 1 - mediates depolarization and excitability (post synaptic)

  • groups 2 and 3 - mediate inhibition of transmitter release (presynaptic)

astrocytes and EAAT in Glutamate synapse

reuptake by excitatory amino acid transporters (EAAT) in the presynaptic terminal and astrocytes (in the astrocyte)

neurotransmitter chemistry

neurotransmitter molecules

• amino acids

• amines

• peptides

• purines

  • ATP is excitatory in the CNS and inhibitory in the gastrointestinal tract

  • Adenosine both excitatory and inhibitory in the brain

Dale principle versus Co-transmitters

Dale’s principle: a neuron has only one neurotransmitter

Co-transmitters: two or more neurotransmitters released from one nerve terminal (an amino acid or amine plus a peptide or purine)

divergence

one transmitter activates more than one receptor subtype and causes a greater postsynaptic response

convergence

different transmitters converge to affect the same effector system

Catecholaminergic neurons

involved in movement, mood, attention, and visceral function

tyrosine - precursor for the three amine neurotransmitters that contain catechol group

• dopamine

  • important in regulating movement

• norepinephrine

  • two types of receptors: alpha and beta

  • is the neurotransmitter of the sympathetic nervous system

• epinephrine (adrenaline)

serotonergic (5-HT) neurons

• amine neurotransmitter - derived from tryptophan

• regulates mood, emotional behavior, and sleep

  • SSRIs - antidepressants

GABA - gated and glycine-gated channels

• GABA mediates most synaptic inhibition in CNS

• glycine mediates non-GABA synaptic inhibition

• bind ethanol, benzodiazepines (increase frequency), and barbiturates (increase duration)

• molecular analysis

  • transmitter-gated (Cl) channels

    • GABA(a) receptors

    • 5 proteins make up the receptor

    • different subtypes: alpha, beta, gamma, delta, and rho (alpha, beta, and gamma are sensitive to ethanol)