Neurons in Synapses Flashcards
Synapses:
Cellular junction where info is transmitted from one neuron to another
Types of synapses:
- electrical
- chemical
Electrical synapses:
- ions passed directly from one cell to another through gap junctions (in heart tissue and smooth muscle)
Chemical synapses:
- majority of synapses in body
- has two cells (pre and post cells)
- also has synaptic cleft w/ ICF between cells
Axondendritic area:
dendrite and axon terminal
Synaptic transmission:
passage of info at synapse
Axosomatic area:
soma and axon terminal
Axoaxonic area:
axon and axon terminal
Neuromuscular junction (NMJ):
skeletal muscle and axon terminal
Synapse en passant area:
smooth muscle and axon terminal
Step 1 in mechanism of signal transmission at chemical signal at presynaptic neuron: terminal ends of axons enlarged
- has neurotransmitter in membrane bound vesicles
- vesicle has set # of neurotransmitters
Step 2 in mechanism of signal transmission at chemical signal at presynaptic neuron: depolarization of axon
- leads to depolarization of axon terminal
- VG Ca2+ channels open
Step 3 in mechanism of signal transmission at chemical signal at presynaptic neuron: Ca2+ enters from ISF down electrochemical gradient
- increase of [Ca2+] inside cell
- helps fuse vesicle to presynaptic membrane, which leads to exocytosis of neurotransmitters
- # of vesicles released is directly proportionate to ICF [Ca2+]
Step 4 in mechanism of signal transmission at chemical signal at presynaptic neuron: end of conduction of impulses
- free intracellular Ca2+ removed from axon terminal by Na+/Ca2+ antiporter pumps
- Na+/K+ ATPase restores membrane potential
- neurotransmitters in cleft are removed and broken down on post synaptic membrane by catabolic enzymes
- reuptake pumps: in presynaptic membrane and recycle/degrade neurotransmitters
Monoamine oxidase (MAO):
breaks down norepinephrine
For CNS, glial cells…
reuptake and breakdown neurotransmitters
Mechanism of signal transmission at chemical signal at synaptic cleft
- physical gap
- has ISF
- neurotransmitter diffuses across b/c of large [ ] diffused from release site to receptor site
Synaptic delay:
time required to diffuse across cleft
Step 1 in mechanism of signal transmission at chemical signal at post synaptic membrane: neurotransmitters bind to receptor
- on neuron/effector tissues
- receptor changes shape and activates coupling mechanism
- activation leads to message to the rest of the post synaptic cell
Active region on membrane has receptors that are:
specific for neurotransmitters
Step 2 in mechanism of signal transmission at chemical signal at post synaptic membrane: signal transduction pathway
- temporarily opens ion channels directly/indirectly
- ions will leave/enter cell, just depends on which channels are open and the electrochemical gradient
Step 3 in mechanism of signal transmission at chemical signal at post synaptic membrane: activation of _____ and _____
cAMP and cGMP
Step 4 in mechanism of signal transmission at chemical signal at post synaptic membrane: activation of one or more ______
intracellular enzymes
Step 5 in mechanism of signal transmission at chemical signal at post synaptic membrane: activation of gene _______
transcription
Neurons have post synaptic potential:
- ionic flow that creates localized voltage change
- magnitude is based on # of ion channels opened
- are graded and nonpropagated, which causes ion current to flow toward axon hillock
Unitary post synaptic potential:
- in neuron
- one vesicle causes flow of current
- not enough to make AP in post synaptic neuron
Excitatory post synaptic potential (EPSP):
- in neurons
- occurs with increased influx of positive ions (Na+)
- depolarizes membrane, which increases the chances of AP
Inhibitory post synaptic potential (IPSP):
- in neurons
- two ways: by increasing efflux of positive ions or by increasing influx of negative ions
- hyperpolarizes membrane, which lowers the chances of AP
T/F: at skeletal muscle junction (NMJ), each axon terminal synapses with multiple skeletal muscles
F, they only synapse with one skeletal muscle
NMJ has end plate potential (EPP):
- is excitatory post synaptic potential
- single release of neurotransmitter makes large EPP
- depolarizes sarcalemma above AP threshold
- will produce spike potential to create contraction
Function of catabolic enzymes
- inactivates/breaksdown neurotransmitters
- are on surface of post synaptic membrane (ACHE, COMT), pre synaptic membrane (MAO), and glial cells (glutamate to glutamine)
- prevents continual stimulation of post synaptic cell
Types of coupling mechanisms on post synaptic cell:
- can affect speed of transmission
- ionotropic
- metabotropic
Ionotropic:
- fast chemical transmission
- neurotransmitters released from small synaptic vesicles near pre synaptic release site
- binding with post synaptic receptor directly activates LGC, which alters membrane conductance of ion
and the post synaptic membrane potential
Metabotropic:
- slow chemical transmission
- neurotransmitters released from larger vesicles are more distant from synaptic cleft
- a specific membrane receptor indirectly opens/closes ion channels
- associated with G proteins
Steps of metabotropic mechanism:
- receptor is coupled to G protein
- amplification of signal through generation of 2nd messengers
- activates multiple pathways and regulates multiple cell functions, which can form kinases and phosphotases
Types of receptors in endocrine:
- catalytic receptors
- linked transcription factors
- cytosolic/nuclear receptors (lipid soluble substances use these)
Two patterns of response inside post synaptic cell:
- agonist
- antagonist
Agonist:
- substrate binds to receptor and promotes change in cell function
- some directly gate ion channels
Antagonist:
- substrate binds to receptor and prevents effect
What are the three subunits of a G protein?
- alpha
- beta
- gamma
Mechanism of G protein at metabotropic pathway:
- neurotransmitter binds to receptor, which activates G protein
- GDP dissociates and binding site opens
- GTP binds to alpha subunit
- alpha subunit dissociates from rest of G protein, which activates many intracellular proteins
T/F: inactive from of G protein has GTP molecule bound to the alpha subunit
F, has GDP molecule bound to alpha subunit
Examples of cascade effects from dissociated alpha subunit:
- open/close of ion channel
- activate/inhibit enzymes and promoters of DNA transcription
Gs protein:
- associated with stimulus receptor
- activates adenylate cyclase
G proteins regulate _________ messengers
secondary
Mechanism of Gs protein:
- adenylate cyclase is activated
- ATP converts to cAMP (2nd messenger)
- activates protein kinase a (PKA), which phosphorylates proteins
- increases Ca2+ influx through membrane channels
Gi protein:
- associated with inhibitory receptor
- inactivates adenylyl cyclase
Gp protein:
regulates activity of enzyme phospholipase C
Mechanism of Gp protein:
- phospholipase C cleaves PiP2
- forms 2nd messengers (IP3, DAG, and Ca2+)
- cascade effect (know what each messenger does)
IP3
- inositol-1,4,5-triphosphate
- activates LG Ca2+ channels on ER
- releases Ca2+ into cytosol
DAG
- diacylglycerol
- stays in membrane
- activates protein kinase C (PKC)
Ca2+
- binds to calmodulin (cytosolic protein)
- forms complex that activates calmodulin dependent protein kinases
- activates PKC
How is G protein inactivated?
- by intrinsic GTPase activity, which hydrolyses GTP
- eventually returns G protein to inactive state
Two types of neurotransmitters:
- low molecular weight
- peptide
- both react with specific receptor
Low molecular weight neurotransmitters (LMW):
- small and rapid acting molecule
- found in all somatic motor and preganglionic neurons of autonomic NS
- ex: acetylcholine, amino acids, biogenic amines
Acetylcholine (ACh)
- most important LMW neurotransmitter
- usually excitatory (produce EPSP), but can be inhibitory (produce (IPSP)
What makes and releases acetylcholine?
cholinergic neurons
- choline-acetyltransferase: creates enzyme
- substrates: acetyl coenzyme A and choline
Acetylcholinesterase:
- degrades acetylcholine
- bound outside postsynaptic membrane
- produces acetate (diffuses away) and choline (reuptaken at presynaptic terminal by Na+ symporter)
2 main receptor types for acetylcholine in CNS and PNS:
- nicotinic (N)
- muscarinic (M1-5)
Nicotinic receptor:
- ionotropic receptor that has ion channel at core
- allows rapid influx of Na+
Muscarinic receptor:
- metabotropic receptor associated with G protein
- activation of M2
Activation of M1 receptor leads to…
- decreases K+ conductance b/c of activation of phospholipase C
- depolarizes membrane
- used in bronchioles
Activation of M2 receptor leads to…
- increases K+ conductance b/c of inhibition of adenylyl cyclase
- hyperpolarizes membrane
- used in SA node
Amino acids:
- LMW neurotransmitters
- glutamate: excitatory transmitter in brain, spinal cord, and eye (ionotropic receptors)
- gamma-aminobutyrate (GABA): inhibitor used in brain
Major inhibitor role of GABA in ______ and _______
basal ganglia and cerebellar Purkinje cells
GABA can be ionotropic or metabotropic:
- ionotropic GABAa receptor: LGC that increases Cl- conductance
- metabotropic GABAb receptor: activates G protein, which increases K+ conductance and can act to inhibit release of neurotransmitter
Biogenic amines:
- LMW neurotransmitter
- made from amino acids
- have NH2 group
- ex: serotonin and catecholamines
Serotonin:
- biogenic amine
- made from tryptophan
- found in brain, spinal cord, and brain stem
- can be excitatory/inhibitory, just depends on coupling mechanism and receptor
- 80% is reuptaken to presynaptic neuron via Na+/Cl- dependent transporter
- rest is reuptaken into glial cells
Functions of serotonin:
- stimulates neurons in sensory perception
- promotes learning and memory
- controls mood
- promotes sleep induction b/c it activates inhibitory neurons in reticular formation
- causes reduced relay of sensory info to cortex
- stimulates interneurons of lateral spinothalamic tract involved in inhibition of pain transmission
Serotonin is broken down by:
- MOA in presynaptic neurons
Catecholamines:
- biogenic amine
- made from tyrosine
- ex: dopamine, norepi, epi
Dopamine:
- type of catecholamine
- mainly inhibitory
- found in brain stem nuclei
- coke: inhibits reuptake
- amphetamines: increase release
Functions of dopamine:
- helps in controlling complex movements and moods
Adrenergic neurons:
- release norepi and epi to brain and effector tissues of ANS
- main excitatory neurotransmitters of sympathetic neurons
Norepinephrine:
- biogenic amine
- binds to metabotropic alpha (preferred) or beta receptors
- alpha 1 receptors: produce EPSP
- alpha 2 receptors: autoreceptor and produces feedback inhibition (inhibits norepi from being released)
How does norepi provide feedback inhibition?
hyperpolarizes axon terminal by opening K+ channels
What happens to norepinephrine after signal is produced?
- 80% reuptaken into presynaptic cell
- degraded in terminal by MAO
- remainder degraded by COMT in synaptic cleft
Epinephrine:
- biogenic amine
- some made from sympathetic neurons
- most come from adrenal medulla
- will bind to both alpha and beta (preferred)
LMW are synthesized in…
presynaptic axon terminals
Central role of acetycholine is in the:
- basal ganglia
- ANS
