Neuro w/neurotransmitters and regulation Flashcards
1
Q
AP arrives
A
- depolarize membrane as AP arrives
- open voltage gated calcium channels which increase in calcium inside presynaptic membrane, which stimulates exocytosis which releases Ach
- more AP then more neurotransmitter
- as > Ach in cleft, there’s > Ach receptors which is ligand gated ion channel
- which > conductance to both Na+ and K+
2
Q
What happens when we get to the axon terminal
A
- neuron and skeletal muscle : motor neuron
- as AP travels down, we open voltage gated Ca+ channels to allow Ca 2+ in which increases its conductance and its concentration inside cell
- Ca 2+ stimulates exocytosis of Ach-containing granules
- Ach releases into cleft and Ach receptor on post-synpatic membrane (ligand gated ion channels) increase conducatnce of K+ and Na+ at same time when activated via Ach binding
- local current flow in skeletal muscle (EPP)
3
Q
End Plate Potential from > Na+ and K+ conductance
A
- motor neurons always gen enough response to dump just enough Ach to generate AP in skel muscle
- EPP is halfway btwn E na+ and E k+
- local current flow around cleft, whcih travels to edge of synaptic cleft where reaches threshold potential to fire AP
- K and Na toward own equilirium and MP in btwn
- sets up local current flow along post-synaptic membrane
- this brings skeletal msucle to AP
4
Q
Ach esterase
A
- Ach esterase degrades Ach so choline goes back into presynaptic side to resynth Ach and acetyl floats away synaptic cleft
- turn over Ach via this enzyme
5
Q
Eserine
A
- drug that inhibits Ach esterase
- dose dependent effect
- low dose of serine will allow more Ach in cleft for longer time therefore potentiate Ach effects
- high does means Ach stays bound, therefore muscle contracts because of continuous depolarization (can’t ventilate lungs)
- wipe out esterase activity; Ach sits in cleft and continually stimulates so problem breathing
6
Q
Diff drugs that can mimic Ach effects : Nicotine and Curare
A
- ex nicotine (Ach AGONIST - binds and activates some cholinergic receptors; by mimicing action of neurotransmitter)
- nicotinic receptors in skeletal muscle, parts of CNS and autonomic NS like certain ganglia
- nicotinic antagonists - agent that bind and block action of Ach receptors
- ex. curare (south am. frogs) - binds cholinergic receptors at skeletal muscle and prey looses coordination
- cobra venom is also antagonist, paralyzes prey
7
Q
Muscarinic Receptors are type of cholinergic receptors
A
- muscarinic receptors bind muscarin which is agonist for receptors found in visceral tissue; places ennervated by parasympathetic NS
- muscarinic receptors not ligand gated but open K+ channels which causes outflow of K+ and hyperpolarizes membrane, since > K+ permeabilit, driving RMP farther from zero so more difficult to stimulate
- Ach binds receptor which activates G protein which turns K+ ion channel on so K+ flows out and then E mem moves b/c K+ leaving
- hyperpolarizes cell (inside becomes more negative)
- atropine is antagonist
8
Q
Receiving end of Nerve
A
- 100s of 1000s of synapses
- excitatory and inhibatory properties
- voltage gated Na+ channels are here and at axon hillock, not cell body
- AP moves down neuron away from cell body not other direction
9
Q
Excitatory psp (EPSP) vs. Inhibitory postsynptic potential (IPSP)
A
- EPSP sets up excitatory local current flow
- common, ex. glutamate and apartate
- they bind receptors and > conductance to Na+ and K+ simultaneously, so move AP closer to zero
- set up local current flow at edge of cell
- IPSP sets up inhibitory local current flow
- glycine and GABA
- glycine > conductance of Cl- ; GABA > conductance of Cl-
- Cl- move into cell and hyperpolarizes cell; sets up local current flow
10
Q
Integration
A
- cells must integrate all local current flows IPSP and EPSP
- local current flow lasts a short period of time
- strongest at input and weaker farther away - decremental
- temporal summation and spatial summation so all integrated together
- key decision @ axon hillock - is there enough local current flow to reach threshold? if so, fire AP down axon since voltage gated channels are in axon hillock so if bring area to threshold then fire AP
11
Q
Neurotransmitters
A
- Ach
- Amines - norepinephrine, serotonin, dopamine
- A.A.
- Peptides - endorphins
- Purines (ATP, AMP)
- gases - nitric oxide
- canabinoids - FFA
- when we fire AP in motor neuron we cause muscle contraction and always fire enough AP to get enough Ach to ensure we get complete muscle contraction but not everything works that way
- nicotinic cholinergic receptor which is ligand gated ion channel, allow Na+ and K+ to come in which gives depolarization
12
Q
Catecholamine Biosynthesis
A
- phenylalanine and tyrosine are neurotransmitters that come from these
- know 3 major catecholamines
- take tyrosine and make DOPA adn from that make dopamine and then norepinephrine (no R group) and then epinephrine (has methyl)
13
Q
Adrenergic Receptors - subtypes
A
- adrenaline, noradrenalin is NE and is signal and 3 types of adrenergic receptors:
- type I: alpha1 via G protein –> > Ca2+ in cell to smooth muscle contracts
- type II: alpha2 –> inhibits cAMP to relax smooth muscle for area surrounding bronchioles
- alpha2 can also block smooth muscle contraction
- type III: beta –> stimulates cAMP, cause smooth muscle relaxation in lungs to open lungs; heart muscle contraction
- take home: response to NT depends on types of receptors at target tissue
14
Q
Norepinephrine
A
- adrenergic synpase release more NE
- take tyrosine and make dopa and make dopamine in secratory granule and make more NE and w/signal you get release NE which binds cleft and binds receptors (adrenergic receptors and diff subtypes which dictate how responds)
- want to stimulate again:
- transporter in presynpatic membrane takes some NE back in although some gets degraded
- when gets back in can recycle or into mito where MAO enzyme degrades NE
- if you inhibit MAO then level of NE > in presynaptic area so packages more and releases more NE
- manipulate things at synapse
- pharmacodynapics - effect drug has on body
- pharmacokinetics - effect body has on drug
15
Q
Serotonergic Synapse
A
- tryptophan hydroxylated to make serotonin (5HT)and put in vescile and release according to AP
- it binds to receptors and 7 major types of serotonergic receptors w/subtypes in GI tract
- do reuptake and can repackage and recycle or degrate in mito w/MAO
-
use reuptake inhibitor and if block reuptake then leave more serotonin in cleft
- get more binding so more activity (law of mass action)
-
use reuptake inhibitor and if block reuptake then leave more serotonin in cleft
-
imipramine is drug that blocks reuptake of NE and serotonin and Prozac just blocks serotonin alone
- takes out lows and helps ppl steady mood; more NE and seratonin in cleft so more binding
- reuptake inhibitors and MAO inhibitors at same time not good
- LSD binds more serotonergic receptors
16
Q
Dopaminergic Receptor
A
- phenyalamine makes DOPA which turns into dopamine (DA) which gets released adn binds to dopaminergic receptors and can be uptake by pre-syn. termina via transporters and recycle or degrade by MAO
- dopaminergic receptors good at down regulating if stimulated a lot begin to pull receptors off membrane so membrane is harder to stimulate so need more dopamine for same level of stimulation
- if take drugs involved in dopaminergic system then receptors down stimulate so need more and more drug for same effect
18
Q
Drugs and Dopamine
A
- methamphetamine: causes big dump of dopamine which make block uptake a bit
- stimulates lots and lots of receptors
- they then down-regulate and take some receptors off cell surface so need more drug for same effect
- cocaine - hydophilic and phobic
- cross bbb easily
- triple uptake inhibitor - inhibits uptake of dopamine, NE and serotonin from synaptic cleft
19
Q
Endogenous cannabinoids are FFA
A
- internal cannabinoid system - more ubiquitous neurotransmitter in brain - they are FFA that you see here AEA and 2AG are released via cells to bind receptors
- cannabinoid system feeds back from post-synpatic cell to pre-synaptic cell to bind receptor on that cell and decrease release of neurotransmitter and we thing important feedback in dev nervous systems
- THC in marijuana is 10x more effective than internal cannabinoids
- worried about effect on dev brain is serious
- teens using marijuana in large amounts that are issues w/memory and executive function and motivation since cannabinoid system in hippocampus and cortex
20
Q
2 cannainoid receptors
A
- 2 receptors CB1 in CNS and CB2 in periphery
- there are other cannabinoid compounds in marijuana like CBD and CBN in addition to THC, some may help w/pain mitigation
- in periphery CB2 receptor is associated w/T cells in immune system and may have important function there
- CB1 is in brain and CNS
