PSL 310 Unit 1: Synaptic Activity

Presynaptic activity steps

1. GP in axon travels to terminal knob and induces GP in knob

2. Voltage-gated Ca2+ channels open

3. Ca2+ (2nd mesenger) stimulates synaptic vesicles that have NTs

4. Synaptic vesicles do exocytosis, release NT into synaptic cleft

Postsynaptic activity steps

4. NT binds to ligand-gated ion channels in postsynaptic membrane

5. Ligand-gated ion channels open

6. Postsynaptic potential generated in the postsynaptic cell, AKA GP

Types of chemical synapses

Cholinergic, adrenergic, GABAergic, glutamergic

Cholinergic synapses

In brain and neuromuscular junctions, contain Ach, excitatory or inhibitory, two types

What are the two types of cholinergic (ACh) receptors?

Nicotinic and muscarinic

Nicotinic receptor

ACh-gated, ionotropic, agonist; allows Na+ in and K+ out due to ionotropic

Muscarinic receptor

ACh-gated, metabotropic, agonist, allows Na+ or Ca2+ in by one, K+ out by another via metabotropic

Ionotropic receptor

Receptor that opens via ligand binding and lets ions in/out

Metabotropic receptor

G-protein coupled receptor, no channel, releases 2nd messenger to activate channel protein

Adrenergic synapses

In CNS and autonomic nervous system, contains catecholamines, excitatory or inhibitory, two types

Catecholamines

Norepinephrine and epinephrine

What are the two types of adrenergic receptors?

alpha-adrenergic receptor and beta-adrenenrgic receptor

alpha-adrenergic receptor

alpha-1 and alpha-2 subtypes, catecholamines are agonists, metabotropic

beta-adrenergic receptor

beta-1 and beta-2 subtypes, catecholamines are agonists, metabotropic

GABAergic synapses

In CNS, contain GABA, only inhibitory, two types

Two types of GABAergic receptors

GABAa and GABAb

GABAa receptor

GABA is agonist, ionotropic ligand-gated Cl- channel, Cl- in means neurons hyperpolarize

GABAb receptor

GABA is agonist, metabotropic, G-protein opens K+ channel downstream, K+ out means neuron hyperpolarizes

Benzodiazepines

Stimulates GABAa channels, hyperpolarizes neurons, reduces neuron activity

Propofol

Anesthetic, opens GABAa, adding gas like sevoflurane holds the GABAa receptors open to allow Cl- in and hyperpolarization

Glutamergic synapses

In CNS, contain glutamate, generally excitatory, several ionotropic (AMPA, NMDA) and metabotropic subtypes

AMPA

Ligand-gated Na+ channel regulated by glutamate, works in tandem with NMDA

NMDA

Ligand and voltage-gated Ca2+ channel, has magnesium ion stuck in it, Na+ coming in from AMPA causes magnesium to be kicked out, glutamate binds, Ca2+ can come in

Ketamine

Anesthetic, inhibits depolarization by stopping stuff coming in, activation of neurons reduced

Spravato

S-ketamine, ketamine enantiomer, reduces depression

Gabapentin

Blocks Ca2+ channels at synaptic terminal, no glutamate release in the first place, for neuropathic pain (pain resulting from neurons)

How nerves stop firing

1. Stop presynaptic neuron activity

2. Ligand-receptor binding releases in 1-2 milliseconds

3. NTs diffuse out of synaptic cleft

4. NTs degraded at synapse

5. Presynaptic knob reuptakes NTs

How are NTs degraded at synapse?

Acetylcholinesterase (AChE) and monoamine oxidase (MAO)

Acetylcholinesterase (AChE)

Degrades acetylcholine at synapse

Monoamine oxidase (MAO)

Degrades catecholamines at synapse

How does the presynaptic knob reuptake NTs?

Presynaptic nerve terminals reuptake NTs

MAOI

MAO inhibitors

SSRIs

Selective serontonin reuptake inhibitors

SNRIs

Serotonin norepinephrine reuptake inhibitor

Parnate

MAOI, blocks degradation of norepinephrine, more in synapse

Paxil

SSRI, blocks serotonin reuptake, more in synapse

Effexor

SNRI, blocks serotonin and norepinephrine reuptake, more in synapse