Neurotransmitters Flashcards
glutamatergic signaling fast facts:
100 billion neurons in the brain
100 trillion- 1 quadrillion synapses
each neuron fires 5-50 hz
involved in all excitatory processes in the nervous system
both psychological and pathophysiological roles
glutamate 90% of these synapses (vast majority of excitatory transmission)
have a number of molecular targets
what are some molecular targets of glutamatergic signaling?
AMPA and kainite receptors (Electrical mediators), Na+ permeable
NMDA receptor (chemical and electrical mediators), Na+ and Ca2+ permeable
metabolic receptors
What are AMPA receptors?
gluatmate-responsive, ligand gated ion channels. are able to provide enough depolarization to allow for an action potential to fire. activate and desensitize fast (<10 ms) mainly permeable to sodium, only slightly permeable to calcium (<4% of total current carried)
what do AMPA receptors function as?
an electrical conductor along dendrites to depolarize the membrane
what do NMDA receptors require?
binding of glutamate and glycine
what are NMDA receptors?
high permeability to Ca2+ (~20% of total current carried, electrical and chemical signaling). can only be open once the membrane has been depolarized (otherwise Mg2+ ions block the channel pore, voltage relieves Mg2+ block around -40 mV) remains active for a prolonged period of time compared to AMPA receptors during a single synaptic event
what are GIRK channels activated by?
directly activated by G proteins or second messengers
what is the point of GIRK channels?
they can lower the membrane potential of a cell by hyperpolarizing
what are the two groups of metabotropic glutamate receptors (mGluRs)
increase NMDA receptor activity/risk for excitotoxicity (mGluR1/mGluR5)
decrease NMDA receptor activity/risk for excitotoxicity (all other mGluRs)
what do phosphorylation (kinases) do?
increase activity
what do dephosphorylation (phosphates) do?
decrease activity
what does PKA major kinase do?
increase NMDA receptor activity
what does calcineurin major phosphate do?
decreases NMDA receptor activity
what is GABA?
a primary inhibitory neurotransmitter of the brain
synthesized directly form glutamate by glutamate decarboxylase
ionotropic (GABAA) and metabotropic (GABAB) functions
what is GABAA’s role in physiology?
primary inhibitory neurotransmitter in brain-> make it more difficult to fire action potential
permeable to Cl- (hyperpolarizing)
located synaptically
number of allosteric sites for a number of drugs and modulators including ethanol, benzodiazepins -> potentiate current (anxiolytic/sedative/anticonvulsant effects)
what is GABAB?
receptor is metabotropic
inhibitory
initiates GI signaling
beta/gamma subunits directly modulate potassium and calcium channel activity
what is glycine?
amino acid neurotransmitter, major inhibitory neurotransmitter of the spinal cord/brain stem
primarily iontropic
what are glycine receptors?
sensitive to strychnine
positively allosterically modulated by ethanol
acetylcholine receptors can be??
ionotopic (nicotinic) or metabotropic (muscarinic)
where are nicotinic acetylcholine receptors found?
at neuromuscular junction for muscle contraction (on muscles)
what do nicotinic acetylcholine receptors do?
moves sodium ions into the cell (changes excitability)
some are permeable to the second messenger Ca2+
desensitizes greatly (PKA and PKC phosphorylation leads to desensitization)
needs constant stimulation for continued contraction
how long do nicotinic acetylcholine receptors typically remain open?
until agonist diffuses away within 1 ms
what is acetylcholine broken down in the synapse by?
acetylcholinesterase into choline and acetate
why is acetylcholinesterase a common pharmacological drug target?
because it’s inhibition increases the amount of acetylcholine available at a synapse
what do muscarinic acetylcholine receptors do?
pathway acts on calcium and potassium channels
hyperpolarizing
inhibited for treatment of Parkinson’s
what is serotonin synthesized from?
tryptophan
what is serotonin involved in?
mood, appetite and sleep
how is serotonin removed?
via synapse by synaptic reuptake
serotonin receptors can be??
metabotropic and ionitropic
serotonin is permeable to?
cations
describe 5HT3 (serotonin) receptors functionally
little pharmacological differences known between subunits
permeable to cations, including Ca2+, however Ca2+ also blocks the channel as it permeates
describe 5HT3 (serotonin) receptors physiologically
receptors distributed throughout the CNS and PNS, mediated excitatory transmission in the amygdala, hippocampus and visual cortex
describe 5HT3 (serotonin) receptors pathologically
activation can lead to anxiety, increased seizure propensity, nausea and vomiting
describe metabotropic serotonin receptors
various subtypes
either increase or decrease cAMP
cAMP activates PKA, which can activate potassium channels
catecholamine neurotransmitters include?
dopamine, norepinephrine, and epinephrine
what kind of receptors are dopamine receptors?
metabotropic
describe dopamine’s involvement in circuitry of the mid brain and basal nuclei
motor behavior (dysfunctional in parkinson’s and huntington’s)
involved in reward
initially thought to play a role in schizophrenia
D1 dopamine receptors are?
Gs stimulatory
D2 dopamine receptors are?
Gi inhibitory
