SYNAPTIC TRANSMISSION AND MUSCLE PHYSIOLOGY

synapse in CNS vs PNS

CNS- to other neuron

PNS- to muscle or gland

3 types of neuron-neuron connections

axodendritic, axosomatic, axoaxonic

what neurotransmitter released by vagus nerve slows the heart

Ach

cells must be equal in size to form a gap junction (T?F)

T

what makes a gap junction?

6 connexins on each cell come together to form a gap junction pore

gap junctions are found in what tissues?

in heart, brain and neuroglia

what is the name of the presynaptic end terminal?

bouton

what proteins hold the pre and post synaptic membranes together? (10nm apart)

CAMs (cell adhesion molecules)

what are neurotransmitters contained in until release by membrane fusion exocytosis triggered by Ca2+ increase?

synaptic vesicles

what causes teh Ca2+ channels to open and allow in Ca2+ to trigger neuroransmitter exocytosis in the presynaptic neuron?

action potential

to exocytose synaptic vesicles what complex docks them at the bouton?

SNARE proteins

what binds Ca2+ and engages SNARE docking proteins?

snaptotagmin

how do tetanus toxin and boutulin toxin harm you?

the toxins are proteases that destroy the SNARE complex which prevents neurotransmitter exocytosis

Tetanus targets what neurotransmitter release?

what symptoms?

GABA by attacking synaptobrevin 2

lockjaw and spastic paralysis

Boutulin targets what neurotransmitter release?

what symptoms?

ACh by digesting SNAP25

flaccid paralysis

what type of receptors are on the post synaptic neuron? (ligand or voltage gated)

ligand gated (the neurotransmitter form bouton is the ligand)

EPSP vs IPSP

ESPS- exitatory postsynaptic potential (move closer to threshold- more pos cell)

ISPS- inhibitory postsynaptic potential (move further from threshold- more neg cell)

synaptic potentials (EPSP and IPSP) _______ in amplitude as they move from denrite→body→axon hillock

decrease

what is the region between axon hillock and the first mylein sheath?

axon initial segment (high density of Na+ and K+ channels where action potential is first produced)

where is the summation of EPSP and IPSPs integrated?

axon initial segment

what is back propagation and what could it be involved in?

when action potential moves back from axon initial segment to dendrites

could be involved in memory and learning

is Ach exitatory or inhibitory at the following locations:

CNS

somatic motor

autonomic

CNS- exitatory

somatic motor- excitatory

autonomic- exitatory or inhibatory

(diff responses to same neurotransmitter due to different Ach receptor varieties)

stimulatory effect of Ach on muscle cell is due to ______ receptors

nicotinic Ach receptor

2 types of cholinergic receptors? (Ach receptors)

nicotinic- on brain, skeletal muscle

muscinaric- on smooth muscles, cardiac muscles, digestive system, glands, brain

what are the two cholinergic receptors named after?

muscinaric- responds to aminita muscaria mushroom toxins

nocotic- respons to nicotine toxins

opening of nicotinic Ach channel allows what ions through?

Na+ in and K+out

(Na+ graient steeper so prodominates and acts as EPSP)

in regard to action potential vs EPSPs describe:

_____________________action potential___________________EPSP________

amplitude

stimulus

initial effect

repolarization

conduction distance

max depolarization

refractory perood

drug effects

__________________action potential___________________EPSP________

amplitude: all or none graded

stimulus depolarization. Ach (neurotransmitter)

initial effect open Na+ channels. open Na+/K+ channel

repolarization by opening K+ loss of pos charge over time

conduction distance distance of axon localized

max depolarization +40mV ~0mV

refractory perood yes no

drug effects inhibited by tetrodotoxin inhibited by curare

what is myasthenia gravis?

autoimmue disease by antibodies attacking the nicotinic Ach receptors of muscle cells, particularly in motor end plates causing muscle weakness

(can be treated by neostigimine and emzucalab drigs that block the enz that degrades Ach to try and allow more to bind because there is fewer receptors)

what effects do the following toxins/drugs have?

botulinum toxin

curare

a-bungarotoxin

asxitoxin

tetrodoxin

nerve gas

neostigmine

strychnine

botulinum toxin- inhibits Ach release

curare- prevents Ach interaction with nicotinic receptor

a-bungarotoxin- binds Ach to prevent Ach binding

saxitoxin- blocks voltage gated Na+ channels

tetrodoxin- blocks voltage gated Na+ channels

nerve gas- inhibits acetycholinesterase in postsynapic membrane

neostigmine- inhibits acetycholinesterase in postsynapic membrane

strychnine- prevents IPSP in spinal cord

what is paralytic shelfish poisoning caused by?

clams and muscles can concentrate the teterotdoxin from pufferfish and then saxitoxin can cause paralysis

if binding of Ach to a nicotinic receptor activates ion channels, what happens if Ach binds to a muscinaric receptor?

activates G-proteins

when Ach binds to a muscinaric receptor and G protein gets activated what happnes?

splits into By and a subunits

thea subunit binds GTP, and By subunit can activate K+channel

ligand binding a G protein directly opens an ion channel (T/F)

F- open indirectly as a result of By subunit dissociation from a-ATP unit

in heart ACh binding to muscinaric receptor does what?

By complex binds to the K+ channels and opens them and heart becomes hyperpolarized producing IPSP- ex. by autonomic nerve fibres ie. vagus nerve

in stomach Ach binding muscinaric receptor causes what?

alpha subunit to dissociate and bind K+ channel which closes them causing depolarization (because balance of K+ in and out no longer)

how many subtypes of muscinaric Ach receptors? why is that useful?

5 types named M1-M5, useful for targeting different drugs to different parts of body

Acetylcholinesterase (AChE) function

breaks bond between Ach and its receptor (nicotinic or muscinaric)- found on the postsynaptic membrane

what does AChe hydrolyze acetylcholine into?

acetate and choline

what drugs and toxins inhibit AChE?

drugs to treat myasthenia gravis (due to lack of ACh receptors, increasing the amount of ACh bound is good), as well as in parkinsons

poisons such as nerve gases and organophosphate pesticides

ACh in the PNS is found at

neuromuscular junctions

what is the postsynaptic membrane called in neuromuscular junction

motor end plate

what is an end plate potential?

EPSP produced by ACh in skeletal muscle fibres

ESPS does wht in muscle?

opens voltage gated channels and produces an action potential which are reproduced down the sacrolemma (muscle PM)

what does the drug curare do?

competes for ACh atatchment to nicotinic ACh receptor and reduces end plate potentials

(used to be used by south american natives to paralyze victim by darts, clinically used in surgery and in electroconvusive shock therapy to prevent muscle damage)

most parasympathetic axons of the autonomic system use ____ as neurotransmitter

ACh

what are cholinergic neurons?

neurons that use ACh as their neurotransmitter

gradation potentials: EPSP vs IPSP in the body and dendrites before the axon hillock determine what about the action potential?

the strength of gradation potentials determines the frequency of the action potentials

(because each action potential is all or nothing, stronger gradation doesnt make action potential any stronger, only more frequent)

what are catacholamine monamine neurotransmitters? what amino acid are they all derived from?

catacholamines: adrenaline, epinephrine, dopamine

all derived from tyrosine

norepinephrine vs epinephrine

norepinephrine is neurotransmitter and hormone

epinephrine is hormone

what amino acid are the following monoamines derived from?

seratonin

histamine

adrenaline, epinephrine, dopamine

seratonin - tryptophan

histamine - histadine

adrenaline, epinephrine, dopamine - tyrosine

why do antihistamines make you drowsy?

histamine can promote wakefulness and alertness in brain

what are two mechanisms that stop the action of monoamines in the synapse?

reuptake of the neurotransmitter molecules into presynaptic bouton

degredation by MAO (monoamine oxidase)

monoamines irectly open ion channels (T/F)

F

monoamines act by second messenger systems (ex. cAMP)

what do MAO inhibitors do?

block degredation of monoamine neruotransmitters to increase action of dopamine, seratonon, norpinephrine and melatonin at synapses.

useful in depression, anxiety, panic disorder, parkinsons

what could MAO inhibiting drugs be dangerous to take with?

cheeses, beans, pickled and fermented foods that containe tryamine which can provoke hypertensive crisis (due to increased norepinephrine by sympathetic axons which stimulates vasoconstriction and cardiac pumping)

what is the function of adenylyl cyclase (adenylate cyclase)

converts ATP to cAMP and PPi

cAMP then activates PKA which causes a downstream cascade to open ion channels

what is the other term for seratonin

5-hydroxytryptamine

how does LSD, mescaline and psilocybin work in cerbral cortex?

activating serotonin receptors

what are SSRIs?

serotonin specific reuptake inhibitors- work to bind the seratonin transporter (SERT) and help keep seratonin there to treat depression

seratonin drugs can have many effects inclusing treatment of what conditions?

anxiety, depression, obesity

what is the name of neurons that use dopamine as a neurotransmitter?

dopaminergic neurons (concentrated in the midbrain)

the dopamine neurons in brain are made into two systems _______ and _______

nigrostriatal dopamine system (motor control)

mesolimbic dopamine system (emotional reward)

what dopamine system effected in parkinsons?

nigrostriatal dopamine system

treated with L-dopa and MAO inhibitors

what dopamine system associated with alcohol, meth and cocaine?

mesolimbic dopamine system

how are parkinsons and schizophrenia related?

drugs used to treat schizophrenia antagonists of S2 dopamine receptor- lead to parkinsons symptomys

drugs used to treat parkinsons such as L-dopa in high concentrations give people iwth parkinsons schizophrenic symptoms

norepinephrine use in CNS vs PNS

CNS- arousal (explains arousal on amphetamines)

PNS- smooth muscle, cardiac muscle, glands

cocaine effects the mesolimbic system how?

by crossing the BBB an blocking dopamine reuptake as well as seratonin and epinephrine, its a triple reuptake inhibitor

also blocks Na+ channels which restricts coronary arteries, raises blood pressure promotes stroke, heart disease, ulcer and kidney dammage

what amino acids act as neurotransmitters?

glutamate (glutamic acid), and aspartic acid

over 80% of ESPS in the cerbral cortex are by what neurotransmitter?

gluatamic acid

the energy needed to transport glutamic acid is a major ATP user in brain

how do astrocytes make increased glucose uptake and increased blood flow to different brain regions?

they take glutamate from synaptic cleft

glutamate binds to what 3 ion channels?

NMDA- memory storage (need glutamate, L serine, and AMPA binding to depolarize NDMA channel by Mg2+ release)

AMPA
kalinate

what are the two inhibitory neurotransmitters of the CNS?

GABA (glutamic acid derivative) and glycine

both ligand gated ion channels for Cl- that hyperpolarize to produce IPSP making it harder for the postsynaptic neuron to reach threshold

where is glycine vs GABA concentrated in the CNS?

GABA- widespread

glycine- spinal cord, brainstem, retina

what are the effects of blocking glycine in spinal cord by strychine?

paralysis of muscles, die from asphyxiation due to being unable to relax diaphragm

what is the most prevalent neurotransmitter in brain?

GABA

what is the disease caused by GABA deficency?

huntingtons disease (neurodegenerative)

benzodiazapines liek valium and xanax treat anxiety and promote sleep how?

binding to GABA receptors and increasing Cl- clow which increases inhibitory effect of GABA

(also can be used in epilepsy)

polypeptides can be neurotransmitters (T/F)

T- neurotransmitters

ex. CCK cholecytokinin produced in brain after meal to promote satiety

ex. substance P mediates sensations of pain

(insulin, somatostatinm ACTH, angiotensin II, endogenous opioids, LHRH, TRH, ADH, are also all suspected neurotransmitters)

same nerve can release many neurotransmitters (T/F)

T- ie. ACh and a neuropeptide depending on which conditions

what are three effects of opiod use?

analgesia (pain relief), feeling of reward, alteration in mood

it is suspected that the pain relifef effects of hypnosis and acupuncture could be blocked by ______

noloxone

(wipes the same receptor as it would when used in opioid overdose)

when the _____ receptor was knocked out in mice, morphine was no longer analgesic

mu

what are three endogenous opioid families?

endophins, enkephalins, dynorphins

overeating in genetically obese mice can be blocked by ____

naloxone (dont get euphoria from eating anymore)

the runners high is not suspected to be from enogenous opioids why?

naloxone doesnt inhibit it

what is most abundant neuropeptide in the brain?

neuropeptide Y

neuropeptide Y increases apetite and is supressed by ______

leptin release

if you knockout neuropeptide Y what happens?

seziures and low appetite

what are endocannabinoids?

short chain fatty acids that are the only lipids that act as neurotransmitters (anadamide and 2-arachindonyl glycerol), bind to the same place as THC, not stored but secreted by neurons because can pass easily through membranes

endocannabinoids are retrograde neurotransmitters meaning what?

they come from the postsynaptic neuron and after neuron is depolarized by excitatory imput it diffuses to the presynaptiic neuron where it binds enocannabanoid receptors to inhibit neirotransmitter release

what are most common GPCR in the brain?

endocannabanoid receptors (affect GABA, glutamate and ACh in many regions)

what activities do endocannabanoid effects strengthen?

eating, drinking, exercise, sex, drugs, memory, learning, motivation

exogenous THC in contrast to endocannabanoids has what effect?

impaired learning, memory, attention, deleterious effect on IQ and scholastic achivement

what is common gas neurotransmitter?

NO (nitric oxide)

not N2O-nitrous oxide- laughing gas

how is NO produced in body?

from arginine

NO is released by the PNS to what organs?

penis, GI, respiratory, cerebral blood vessels (causes relaxation)

CO and H2S are both poisonous at higher than physiological levels, but what do they do in body normally?

CO- like NO stimulates cGMP production and potential olfactory stimulation

H2S- also support physiological function in small amounts produced by body

what purines are neurotransmitters/ cotransmitters sometimes?

ATP and adenosine

what can ATP and adenosine bind to? what are they involved in?

purigenic receptors

blood clotting, taste, pain, caffine effects

insertion vs removal of AMPA recptors effect on synapic transmission

insertion of AMPA- long term potentiation of synapse- learning and memory

removal of AMPA- long term depression of synapse-

(contribute to synaptic plasticity)