1.2 Amino Acid CNS Neurotransmitters

Briski

acidic amino acids lead to which type of potentials?

excitatory (EPSPs)

how do acidic amino acids lead to EPSPs

they increase Na conduction in postsynaptic membranes which leads to depolarization (AP)

what are the two of the most common acidic amino acids that cause EPSPs?

glutamate (Glu) and aspartate (Asp)

what is the most abundant CNS amino acid NT

glutamate

glutamate is responsible for ___ of excitatory neurotransmission

75%

glu or asp injected into the brain leads to…

seizures

glu and asp are both charged so they ______ (do or do not) cross the BBB

do not

True or false:

glu and asp must be made from precursors in the neuron

True

explain glutamate synthesis

glutamine is converted to glutamate via glutaminase (which is a reversible process via the same enzyme)

is glutamate synthesis reversible

yuh

glutamate and aspartate both activate which receptor families?

ionotropic and metabotropic

ionotropic receptors

upon NT binding, directly open ion channels

examples of ionotropic receptors

NMDA, kainate, AMPA

what are some agonists for NMDA receptors

NMDA

Asp

Glu

glycine

NMDA receptor agonist effects

increases Na conduction causes slow and long duration depolarization (AP)

NMDA receptor agonists lead to increases in the conduction of _____ into the neuron

Na

NMDA receptor agonists lead to ____ and _____ duration of depolarization

slow and long

what are some kainate receptor agonists

kainate, ATPA, and glutamate

what is the effect of kainate receptor agonists

increases Na and Ca conductance which leads to fast and short depolarization

kainate receptor agonists lead to increases in the conduction of ____

Na and Ca

Kainate receptor agonists lead to ___ and ____ depolarization

fast and short

AMPA receptor agonist examples

glu, kainate, and quisqualate

AMPA receptor agonist action

fast and short duration of depolarization, increases Na and Ca influx

AMPA receptor agonist leads to ___ and ___ depolarization

fast and short

AMPA receptor agonist leads to increase conduction in _____

Na and Ca

which receptor is activated by the simultaneous binding of 2 agonists

NMDA

NMDA receptors are activated by the simultaneous binding of which two agonists

Glu and Gly

NMDA receptors have binding sites for…

ketamine and PCP

ketamine and PCP act as ______ on NMDA receptors which leads to ____

noncompetitive antagonists, impairing cognitiion

chronic PCP exposure leads to…

excessive glu neuronal activity which leads to hallucinations

excessive glu activity leads to

hallucinations

kainate receptor dysfunction is associated with which disorders

epilespy, huntingtons, autism, and schizophrenia

the function of the ____ receptor is unclear in pts who are healthy

kainate

which receptor antagonists show promise for neuroprotective agents in the treatment of stroke

AMPA

AMPA receptor antagonists have promise to be…

neuroprotective agents for the treatment of stroke

AMPA receptor _____ (agonists or antagonists) has promise for being a neuroprotective agent for treatment of stroke

antagonists

metabotropic glutamate receptors are which type of receptor

GPCR

what are the classes of metabotropic glu receptors

group I, group II, group III

what are the members in metabotropic glu receptor group I

mGluR1 and mGluR5

what are the members in metabotropic glu receptor group II

mGluR2 and mGluR3

what are the members in metabotropic glu receptor group III

mGluR4, mGluR6, mGluR7, mGluR8

where are metabotropic glu receptors located

on pre and post synaptic membranes

presynaptic metabotropic glu receptors are associated with…

decreasing both excitatory (Glu) and inhibitory (GABA) synaptic transmission

presynaptic group II metabotropic glu receptors are targets for…

drug development of anxiety disorders, schizophrenia, and epilepsy

which group of metabotropic glu receptors is a target for the development of treatment for anxiety disorders, schizophrenia, and epilespy

group II (mGlyR2 and mGluR3)

decreases in acidic amino acid neurotransmitters leads to ______ diseases

neurodegenerative

examples of neurodegenerative diseases

alzheimers, dementia

decreased acidic amino acid neurotransmitters leads to impairments in…

learning, memory, and cognitive functions

increased acidic amino acid neurotransmitters can lead to…

spasticity and schizophrenia

neutral amino acids lead to ____ potentials

inhibitory

IPSP

inhibitory post synaptic potential, makes neuron less likely to have a AP

neutral amino acids cause increased conductance of ____

K and Cl

neutral amino acids lead to _____-polarization

hyper

what is the main neutral amino acid in the CNS

GABA

GABA stand for

gamma aminobutyric acid

where does GABAergic inhibition occur in the CNS

hypothalamus, hippocampus, cerebral cortex, and cerebellar cortex

_____% of CNS inhibitory synapses involve GABA

50

GABA is formed by the ___ of Glu

decarboxylation

GABA is formed by the decarboxylation of ____

Glu

which enzymes are able to decarboxylate glu to GABA

glutamic acid decarboxylase and vit B6

is the process of turning glu to GABA reversible or irreversible?

irreversible

vitamin B6 deficiency can result in…

neuronal hyperactivity, seizures, and convulsions

____ deficiency can lead to neuronal hyperactivity, leading to seizures and convulsions

vitamin B6

what are the two kinds of GABA receptors

GABAa and GABAb

GABAa receptors are ____ which GABAb receptors are _____

ionotropic, GPCR

where can you find GABAa receptors in the CNS

cortex, basal ganglia, and hippocampus

where can you find GABAb receptors in the CNS

cerebellum and spinal cord

GABAa receptor electrophysical response

hyperpolarization and increase in Cl influx

GABAb receptor electrophysical response

hyperpolarization, increase K efflux and decreases Ca influx

both GABA subtype receptors lead to _____-polarization

hyper

GABAa receptors lead to increased ____ influx

Cl

GABAb receptors lead to increased ____ efflux and decreased ___ influx

K and Ca

example of a GABAa receptor agonist

muscimol

example of a GABAb receptor agonist

baclofen

example of a GABAa receptor antagonist

bicuculline and picrotoxin

example of a GABAb receptor antagonist

phaclofen

muscimol is an example of…

GABAa agonist

baclofen is an example of…

GABAb agonist

bicuculline and picrotoxin are both…

GABAa antagonist

phaclofen is an example of

GABAb antagonist

associated structures to GABAa receptors

benzodiazepine and barbiturate binding sites

what are some conditions related to GABA neuronal dysfunction

extrapyramidal disorders

spasticity

epilepsy

degenerative states

psychosis

anxiety

alcoholism

addictions

sleep disorders

examples of extrapyramidal disorders due to decreases in GABA

parkinson’s, huntingtons, and neuroleptic drug induced tardive dyskinesia

spasticity is due to _____ (increased or decreased) GABA

decreased

examples of GABA mimetic drug

benzodiazepines

benzodiazepines are used as…

anti-spasmodics and muscle relaxants

explain GABA’s effect on epilepsy

drugs that block GABA can lead to convulsions where drugs that increase GABA action can prevent seizures

explain GABA’s effect on degenerative states

destruction of GABA neurons is associated with pre-senile and senile dementia

explain GABA’s effect on psychosis and anxiety

decreased GABA transmission is associated with thought and emotional disorders

GABA antagonists are also called…

convulsants

GABA antagonist examples

bicuculline and picrotoxin

GABA agonist/enhancers are also called

anticonvulsants

GABA agonist example

vigabatrin

vigabatrin is a…

a. GABA agonist

b. Glu agonist

c. GABA antagonist

d. Glu antagonist

a

Glycine is expressed at high levels in which areas of the CNS

spinal cord, lower brain stem, and gray matter

activation of Gly receptors leads to… (EPSP or IPSP)

IPSP

activation of Gly receptors leads to an increase in the conduction of ____

Cl

activation of Gly receptors leads to an ______ in the conduction of Cl

increase

glycine is antagonized by…

strychnine and tetanus toxin

what are some poisons that induce seizures

strychnine and tetanus toxin