neurotransmitters Flashcards
chemical communication is used to transmit signals in the nervous system
Differentiated by : distance between transmitting and recieving cells, types of signaling evoked, stability of the transmitting molecules
NT-> synaptic signaling
Nmodulator-> paracrinesignaling
Hormone-> endocrine signaling
fast and short changes in synaptic membrane potential
mediated by ligand-gates ionotropic receptors
changes in ionic conductnce that result in changes in membrane potential
EPSP or IPSP
Summation of these potentials regulates probability of AP generation
slow and long lasting membrane potentials
mediated by GPCRs- direct interactions between a channel and the G protein subunit, and indirect as a result of changes in phosphorylation triggered by 2nd messengers
Both depolarization and hyperpolarization
Tend to take longer to develop last longer than ionotropuc receptor signaling
acetylcholine
synthesized from choline and acetyl CoA via choline acetytransferase (ChAT)
Ach is put into vesicles via VaChT
metabolized bye acetylcholine esterase (AChE) a very efficient enzyme especially at the neuromuscular junction
Choline is taken back into the button- RATE LIMITING STEP
cholinergic receptors
Nicotinic (fast)- bound by nicotine as well, ligand gated Na channel, located at neuromuscular junction, preganglionic synapses, rewards and arousal circuits in the brain
Muscarinic (slow)- bound by muscarine, member of the GPCR family, located at parasympathetic ganglia, basal forebrain, striatum, blockers of muscarinic receptors are used to treat parkinsons disease
glutamate
synthesis and degredation are linked through the glutamine/glutamate shuttle
Invovles membrane carriers on both astrocytes and neurons also carry aspartate
Packaged into vesicles via the VGlut family of carriers
Mechanisms promote sustained supply; fast release; and quick removal from the synapse
Glial cells help take up the glutamate and convert to glutamine (gulatmine synthase) that can be taken up and turned into glutamate (glutaminase)
receptors for glutamate
all are ionotropic
AMPA and kainate receptors: Na is the primary ion, activation results in epsp, primary mechanism for excitatory information flow from point to point in the CNS
NMDA receptors: require both glutamate to bind and membrane depolarization to open, calcium as well as sodium is conducted, NMDA receptors are required for long term potentiation, learning and memory
Excessive amounts of glutamate are toxic to neurons. Too much glutamate can injure or kill neurons due to calcium entry via NMDA receptors which activates proteases and ATP is depleted trying to get rid of it
Stroke: anoxia triggers release of excessive amounts of glutamate
in neurodegenerative disorders glutamate reuptake is reduced
NMDA receptor inhibitors are used to treat AD and ALS
gaba
GABA is the major inhibitory NT in the CNS (glycine) in point to point information flow in striatum and cerebellum
interneurons throughout the CNS
GABA is synthesized from glutamate by GAD, vitB 6 is an essential cofactor (glia and neurons)
GABA receptors
GABAa receptors are ionotropic conduct chloride Cl- produce IPSP
Many allosteric binding sites in the receptor complex, site of action of ethanol, general anesthestics, valium barbituates
GABA b receptors are GPCRs, results in hyperpolarization via potassium channel opening
biogenic amines
slower onset and offset changes in synaptic potential, mediated by the biogenic amines (dopamine, NE, 5HT, histamine)
Act via GPCR
brsin stem and hypothalamus, project widley
life cycle of biogenic amines
all start from amino acids (Dope and NE from tyrosine), serotonin from trp, Histamine from histadine
Enzymes are found in the axon terminal regions, synthesis is regulated by product and presynaptic receptors
Stored and released from synaptic vesicles
inactivated by selective carier mediated reuptake and ezymatic breakdown
Reuptake carriers for biogenic amines
serotonin reuptake transporter (sert) =target of serotonin selective reuptake inhibitors for depression
Dopamine re trans (DAT)= target of cocaine-amohetamine
NE reuptake transporter (NET)=target of tricyclic antidepressants
biogenic amines play distinctive role
NE-autonomic outflow in brainstem sympathetic ganglia arousal, roles in blood pressure regulation and attention
Dopamine- regulates reward extrapyramidal system, roles in addiction and parkinsons disease
Serotonin- regulates sleep/wake, mood, role in depression
Histamine- regulates sleep/wake, vestibular function
neuropeptides as signaling molecules
energetically expensive, low amounts released, perhaps in compensation,affinity is high
inactivation via peptidases
