Advanced Physiology Exam I Topic 3

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Topic 3
updated 8 years ago by dante1
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1

synapse

the cellular mechanism where a neuron communicates with another cell

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synaptic transmission

the name for the process where an AP arrives at a synapse...triggers the synapse...causes a signal to be transmitted to another cell

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presynaptic cell

the cell sending the signal (always a neuron...end of axon ends in a selling with the synaptic terminal)

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postsynaptic cell

the cell receiving the signal (most are neuron (motor systems))
*somatic motor system...postsynaptic cells are skeletal muscle cells
*autonomic motor systems...postsynaptic are cells of internal organs

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synaptic cleft

narrow space separating the presynaptic cell and postsynaptic cell

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synaptic transmission (the process)

depolarization at synaptic teminal of presyn cell...chem neurotransmitter is released from presyn into syn cleft...chem bind to receptors on postsyn cell and activates receptors...activated receptors have effect on physiology of postsyn cell

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synaptic vessicles

vesicles containing a signaling molecule

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neurotransmitter

signaling molecule contained in the synaptic vessicle

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key concept: each neuron only makes one neurotransmitter...

example...glutamatergic cell as a neuron that has glutamate

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Voltage gated Ca channels

gated channels whose gate opens when Vm exceeds -50mV
E(Ca) is around +130mV so when Ca gates open at Vm=50mV, theres a huge inward drive of Ca into the synaptic terminal

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Action of Ca

binds to a protein complex connected to synaptic vesicles...causes the vesicles to fuse with the membrane and release their contents into the cleft

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reuptake transporters

bind to teansmitter molecule and absorb it back into the synaptic terminal
two effects:
1. allows some neurotransmitter to be recycled
2. helps remove neurotransmitter from the cleft

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receptor molecules

membrane-bound proteins that can bind to neurotransmitter released by the presyn cell which cause some effect on postsyn cell

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degrading enzyme

breaks down neurotransmitter molecules into inactive components (helps reduce neurotransmitter levels after initial release...similar to reuptake)

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three factors that determine the size of a cell's response to any chemical signal

1. the concentration of messenger (concentration of neurotransmitter)
2. the number of receptors present on postsyn cell
3. the affinity of receptors for the messenger

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1. Neurotransmitter concentration

presyn cell release a lot of neurotransmitters into the synaptic cleft...must be removed or destroyed

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2. Number/density of receptors

density (how tightly packed postsyn membrane is with receptors)
has intermediate density allows for:
1. upregulation...increase synaptic strength/density of receptors
2. downregulation...decrease synaptic strength/density of receptors

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downregulation and tolerance

chronic use of a drug leads to downregulation of the receptors, which leads to a reduced effect of the drug

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divergence

where each CNS neuron makes synaptic connections to many other neurons

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convergence

where each CNS neuron receives synaptic inputs from many other neurons

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Key Concept regarding AP in the postsyn cell

in order to achieve an AP, multiple inputs are required through:
*temporal summation--multiple inputs from a single neuron occurring in brief span of time
*spatial summation--inputs from multiple neurons occurring in a narrow time window

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3. Affinity of receptor for neurotransmitter

most post-syn receptors have a very high affinity for neurotransmitters released by presyn cell (low affinity for other molecules)...receptors of synapses tend to be very specific

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key exception for affinity of receptors in the sympathetic nervous system

because this system uses NE and Epi which are bound by adrenergic receptors, making them nonspecific.

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agonists

mimic molecules that activate the receptor and bind at any site

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partial agonists

mimic molecules may only partially activate the receptor

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antagonists

mimic molecules inactivate the receptor

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NMJ and receptors

each postsyn muscle cell gets synaptic input from just one neuron...which releases ACH as it neurotransmitter

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ligand gated (ionotropic receptors)

gate opens when the portein binds to a particular ligand
*channel proteins that are selective for specific ions
*closed in absence of neurotransmitter, open when one binds

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advantage of ionotropic receptors

very fast

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disadvantage of ionotropic receptors

a. activation of the receptor always has same effect on postsyn cell (same ion flow)
b. effect of activating one receptor is small...need to activate many receptors to get big effect on postsyn cell
c. effect lasts only as long as neurotransmitter is present

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intracellular-pathway-linked receptors (metabotropic receptors)

not channel proteins, but instead the receptors are bound to an intracellular protein complex called G protein

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G-protein

a complex of three subunits: alpha, beta and y
When neurotransmitter binds to receptor, G protein dissociates from receptor causing alpha subunit to dissociate from other subunits and replacing GDP with GTP, then binds to effector protein and triggers cellular response

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2 main types of metabotropic receptors

1. direct coupling--activated alpha subunit binds to a channel protein and causes it to open or close
2. second messenger system--activated alpha subunit binds to and activates an enzyme which triggers other effects

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2 common second messenger pathways

1. Adenylate cyclase pathway...alpha subunit activates adenylate cyclase, converting ATP to cAMP, which increases and activates enzyme protein kinase, changing the behavior
2. phospholipase C pathway...alpha subunit activates phospholipase C and coverts PIP2 to DAG and IPx which moves into cell and causes the release of Ca

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key concept of metatropic receptors

often include multiple pathways at once and the effects are widespread

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disadvantage of metatropic receptors

effects are slow with direct coupling being faster than second messenger

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advantages of metatropic receptors

1. long duration of effect
2. flexibility--lots of different effects are evoked in the cell
3. amplification (KEY) resulting in positive feedback
**in all advantages, second messenger work better than direct coupling

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ionotropic vs metabotropic

speed: ionotropic greater than direct coupling metabotropic which is greater than second messenger metabotropic
Duration, flexibility, and amplification: second messenger metabotropic is greater than direct coupling metabotropic which is greater than ionotropic

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exitatory receptors

increase the chance that postsyn will generate an AP

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inhibitory receptors

decrease chance that postsyn will generate AP

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excitatory postsyn potential (EPSP)

depolarizing change in Vm

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inhibitory postsyn potential (IPSP)

hyperpolarizing change in Vm (ER < Vm)

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ER (equilibrium potential for the receptor channel)

is the membrane voltage (Vm) required to get no net flow of ions through the channel (the preferred voltage of the channel)
**Vm<ER then net inward flow of positive ions or outward flow of neg ions and drives Vm up toward ER
**Vm>ER then outward flow of pos ions or inward flow of neg ions, drives Vm down toward ER
Thus, the opening of receptor channels drives the cell toward ER

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Intuitions of ER

activating receptor channels moves the Vm toward ER and the more channels activated, the bigger the effect on Vm

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glutamate (an amino acid)

in the CNS (brain and spinal chord), the main excitatory neurotransmitter...over 80%

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AMPA receptor

most common typs of glutamate receptor

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long term potentiation (LTP)

the more excitatory stimulation a synapse receives, the stronger the excitatory synapse becomes----positive reinforcement

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NMJ transmitters and receptors

ACh as neuro and nAChR as receptor

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inhibittory receptors work in two ways

induce hyperpol gaded potential (IPSP)
they clamp a cell's Vm near rest and cancel out EPSP thus reducing chance of AP

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4 neuromodulator systems

NE, Serotonin, Dopamine, Aceylcholine

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autoreceptors

receptors that bind to the transmitter that is released at the synaptic terminal
tend to have inhibitory effect on synaptic teminal...function as negative feedback

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heteroreceptors

receptors that bind to other transmitters--generally because a differeent neuron forms a synaptic contact at that point...a presynaptic synapse

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heteroreceptors (presynaptic facilitation)

the input has an activating effect on the presynaptic terminal...increases the amount of transmitters released

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heteroreceptors (presynaptic inhibition)

the input has a suppressing effect on the presynaptic terminal

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PSNS releases this neurotransmitter onto target cell

ACh

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SNS releases this neurotransmitter onto target cells

NE

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muscarinic cholinergic receptors

receptors for ACh and PSNS (two major types: activating and suppressing)

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activating cuscarinic cholinergic receptors

when activated...activate phospholipase C pathway...increase Ca (mostly in smooth muscle cells and the increase in Ca causes cell to contract)

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suppressing muscarinic cholinergic receptors

when activated...alpha subunit of G protein binds to a K channel...opens it...inhibits membrane voltage in the postsynaptic cell, which suppresses activity

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adrenergic receptors

receptors for NE and Epi (four subtypes (two activating and two suppressing)

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alpha 1 adrenergic receptors (activating)

when activated...activate phospholipase C pathway...increases Ca (mostly in smmoth muscle)
Epi binding

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alpha 2 adrenergic receptors (suppressing)

when activated...reduce adenylate cyclase activity...reduce cAMP lvls...reduce protein kinase activity
function as autorecptors on presyn of SNS (turn down activity from NE)
function as inhibitory heteroreceptors on PSNS
Epi binding

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beta 1 adrenergic receptors

increase adenylate cyclase activity...increase cAMP...increase protein kinase activity (Epi binding)

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beta 2 adrenergic receptors

suppressing...when activated, increase adenylate cylase activity...increase cAMP...increase protein kinase activity
Epi binding