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TULANE / Neuroscience / NSCI 3310 / Why is the inside of a neuron negatively charged?

Why is the inside of a neuron negatively charged?

Why is the inside of a neuron negatively charged?


School: Tulane University
Department: Neuroscience
Course: Cellular Neuroscience
Professor: Jeffrey tasker
Term: Summer 2015
Cost: 50
Description: So apparently people have been having troubles accessing the other study guide - I've re-posted this one for you guys.
Uploaded: 10/10/2015
25 Pages 454 Views 7 Unlocks

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Action Potential Propagation 10/10/15 9:07 AM

Why is the inside of a neuron negatively charged?

• conduction of AP:  

• action potential = CHANGE IN PERMEABILITY of membrane

• generated at axon hillock

• passive spread of cations through axon

• depolarization of membrane:

o opening of channels create more permeability

• crosses threshold – voltage gated sodium channels open

• in initial segment: influx of Na+ - positive charge spreads  

passively BOTH downstream and upstream (passive  

depolarization on both sides of initiation side)

• downstream flow charges next segment of axon: + charge  

depolarizes this segment to threshold

What is responsible for the absolute refractory period?

• voltage-gated Na+ channels open, passive spread both  

downstream and upstream

• AP REGENERATING – all-or-none

• when charge goes upstream: does not generate AP due to the  absolute refractory period

• those voltage-gated sodium channels are INACTIVATED –

WILL NOT flux current  

• cannot cause any more sodium to go in until membrane  


• prevents back propagation We also discuss several other topics like ­ what social purpose does the belief that race is biological serve for race relations?

• if you stick electrode into MIDDLE of axon (inject positive charge): • sodium will fan out and depolarize membrane BOTH upstream  and downstream ???? backpropagation and forward

How does action potential spread through an axon?

Don't forget about the age old question of Why do we treat children as a special audience?

▪ antidromic spikes

▪ this is experimental, unknown if can occur naturally

• no one is ever at equilibrium – steady state at resting potential • set up combination of active and passive properties

• active voltage-gated sodium channels

• passive fan out of charge

• propagation of the action potential We also discuss several other topics like How does conditional probability differ from ordinary probability?
If you want to learn more check out How do you find the domain of a polynomial graph?

• orthodromic: action potential travels in one direction (down axon to  the axon terminal)

• antidromic  

o axon: ONLY experimental – antidromic spike

o backpropagation CAN happen in dendrites:

▪ so much positive charge coming in, some makes it to  


▪ this can result in dendritic nt release in certain cells  

(with nt packaged in vesicles INSIDE dendrites)

???? influences nt release for synapse from presynaptic  


▪ depends on number of voltage gated channels,  

leakiness in dendrites

• typical conduction velocity:

o unmyelinated axon: 2m/s

o myelinated: 120 m/s

• duration of AP: around 2ms

• factors influencing conduction velocity:

• axonal diameter (bigger=faster)

o ex: pain receptors in skin:

▪ C fibers – unmyelinated pain and temperatures

???? thin and unmyelinated – SLOWEST We also discuss several other topics like What does thermal energy depend on?

▪ other pain fibers – thin but myelinated – faster  

▪ touch sensors are faster – pain comes later (ex: when  

touching hot pan)

• myelin: layers of myelin sheath facilitate current flow

o myelinating cells:

▪ Schwann (PNS) – take entire body and wrap it around  

axon (one to one)

▪ oligodendrocytes (CNS) – has branches that can wrap  

around segments of 3 or 4 separate axons  

• saltatory conduction: myelinated axons We also discuss several other topics like What is the ability to perceive emotions called?

• nodes of Ranvier – unmyelinated segment in between myelin o high voltage-gated Na channel density

▪ can generate action potentials

• full number of potassium channels

o increased membrane capacity (Cm)

▪ high capacity to store charge (only one lipid bilayer  

separating inside and outside)

o conduction slows

▪ lots of charges to interact with, so takes longer to get  


• internodes - myelin

• thin layers of cell membrane  

▪ virtually no charge in the inner layers myelin

▪ very little interaction between charges inside and  


• charges on inside of cell very separated form charges on  outside of myelin  

• fewer Na channels (low density of Na channels)

• decreased membrane capacity (Cm)

▪ low capacity to store charge (because insulated by  


• charges “jump” to next node

• rapid conduction – not many charges to interact with so they  can rapidly go through

• demyelinating diseases:

• multiple sclerosis: multiple CNS sites

o “many scars”

o one of the most common diseases in CNS

o inflammatory demyelinating condition

o some of the charge escapes

o disrupts conduction of electrical impulses to and from brain o effects speed and efficiency with which impulses are  


o effects smooth, rapid and coordinated movement

o sites where myelin is los ???? plaques or lesions

▪ scars in brain and spinal cord

• Guillain-Barre disease: PNS

o sensory and motor nerves

Passive Properties (aka Cable Properties) 10/10/15 9:07 AM

• Passive vs. Active propagation

• synaptic potentials = passive propagation

o once current reaches

o change in shape and decreased amplitude with distance

• action potentials = active propagation

• no change in shape or amplitude with distance, all or none ▪ because generated and regenerated entire axon length

• conductance (g) – “acceptance” of current flow

• inverse of resistance (1/R)

• more open channels = higher membrane conductance

• factors that govern passive conduction in neurons

• 1. membrane capacitance – charge accumulation on membrane o capacitance (C) - capacity to store charge

o based on surface area

▪ bigger surface = more capacitance

o opposite charges “hold” each other in place across membrane o specific membrane capacitance (Cm) – measured in Farads

▪ charge accumulation per cm2 of membrane

• 2. membrane resistance  

o resistance (R) - resistance to current flow

▪ function of number of channels in membrane  

???? no channels = infinite resistance

???? many channels = little resistance

o inverse of conductance (1/g)

o specific membrane resistance (Rm) – measured in Ohms

▪ resistance of total plasma membrane per cm2 

• 3. axial resistance – resistance of cytoplasmic axis  

• measured in Ohms

o axis = CENTER of whatever you’re looking at

▪ resistance on INSIDE of cable

• membrane is equivalent to an RC circuit

• has resistance – keeps certain charge in

o capacitor = membrane capacitance

▪ responsible for membrane voltage

▪ capacitative current

• resistor: membrane resistance

▪ leak channels

▪ leak current

• battery: membrane potential

▪ potential to generate current

▪ separation in charge between two poles – current  

created when poles are connected

• introducing (+) charge – fans out  

• some goes to membrane to depolarize

• positive charges held outside pushed away

• creates flow of charge – nothing actually crossing membrane  ???? capacitative charge

• some charge leaks out through channel – creates ionic  


• membrane current = Ic + Iionic 

• capacitative current + ionic current

• magnitude of passive membrane potential response is determined by  membrane resistance

• Ohm’s Law: V = IR or ΔV = ΔIR

o determines membrane excitability

o change in voltage proportional to change in current

• under resting conditions – membrane resistance is stable • membrane potential change (passive) in response to current injection (or membrane current) is function of membrane resistance  • a neuron will respond to larger current with a greater change in  membrane potential (proportional)

o passive response will be bigger

• I-V (current – voltage) curve is linear (current – voltage) – because  proportional

• until you reach threshold (while it stays passive)

• if you change R (by opening or closing channels), this relationships  is changed  

• kinetics of passive membrane response is determined by membrane time  constant

• membrane time constant (τ) – determined kinetics of membrane  potential change in response to current injection

o speed of membrane charging/discharging

▪ function of resistance and capacitance (Rm and Cm)

▪ funtion of open channels and ability to store charge

▪ τ = Rinput*Cm (measured in ms)

• exponential decay

• TIME to charge 63% of Vmax OR to discharge by 63% (discharge TO  37% of Vmax) – IN ONE POINT IN SPACE

• determines rate of passive change in potential

• if T = 10, will take 10ms (in that point in space) to decay by  63%

• if T = 1ms, takes 1ms to degrade by 63% in that point in  space

• long τ = slow response

• short τ = fast response

• important in terms of cell’s integration over time of received inputs • axonal/dendritic membrane = series of RC circuits

• each segment can be modeled as equivalent of electrical circuit • resistor (number of open channels) and capacitor (storage of  charge in lipid membrane) in parallel (creates a voltage across  membrane)

• ra = axial resistance over 1cm

• rm = membrane resistance/unit length of cylinder

• if current is introduced,  

o charges membrane capacitance (changes potential)

o some charge leaks out through membrane resistance

o some continues down through axis of cable to next segment o this repeats – with each successive segment, there is less  charge to change capacitance (smaller change in voltage)

• passive signal transmission:

• constant velocity  

• signal decreasing is function of time constant (time it takes to  decrease by 63% (to 37%)  

• time constant etermines how signal is integrated (how it changes)  over time

• distance travelled by passive membrane response is determined by  membrane length constant

• length constant (λ): distance of passive current spread


o exponentially decays with distance travelled (graph is  inverse exponential)

o function of:

▪ 1. axial resistance (ra)

▪ 2. membrane resistance (rm)

???? λ = √(rm/ra)

???? ratio of membrane resistance versus axial  


???? distance traveled to decay by 63% or to 37% of  


• greater λ will travel greater distance (signal going farther) ▪ bigger at each successive segment in membrane (starts  off larger – each one will be larger because same  

amount is leaked)

• cell with larger length constant MUCH more excitable because  maintain magnitude and amplitude over longer distance

• still degenerative signal  

• dendrite is studded with synapses – signals at different times are  generated by all those synapses

• physiological impact of length constant:

• red neuron: lambda = 1mm (travels 1 mm before decaying by 63%) • blue neuron: lambda = .1mm (travels .1 mm before decaying by 63%) • SO red much more excitable, more likely to generate AP in response to  any given input

• Test question examples:

• cell has .1mm length constant with threshold of 5mV above resting  potential

o start at 10mV, 1 length constant away from axon hillock o will cell generate AP???

o NO – it will be 3.7 mV (smaller by 1 length constant) – does  not reach threshold

• if 2 excitatory synapses, both 1 length constant away (same  properties)

• YES – converge on axon hillock and summate to make 7.4 mV (which reaches threshold)

• 10 mV EPSP, 1 length constant away from axon hillock (generated  at time=0)

• 2nd EPSP 1 length constant away BUT generated 1 time  constant later (t=10ms)

• 1st EPSP: 3.7 mV when reaches hillock BUT waits for 1 time  constant so decays another 63% ???? 1.3 mV

• 2nd: 3.7 mV at hillock ???? 3.7 mV

• summation: 5mV which is exactly threshold

• 2 forms of integration

• temporal: time-dependent

• function of time constant

• change over time in one point in space

• spatial: function of length constant

• changes over distance travelled

Synaptic Transmission 10/10/15 9:07 AM

• 2 types of synaptic transmission

• 1. electrical synapse:

o gap junction:  

▪ electrotonic coupling (passive spread of charge in living  


▪ direct current spread between pre and post synaptic

???? ions can flow directly

▪ rapid communication

▪ passive transfer of charge

▪ cytoplasmic bridge between one cell and another

▪ provides resistance to charge transfer between cells  

(more channels = less resistance)

▪ half of channel is provided by each cell (hemichannels)

???? hemichannel is connexon (each cell provides ONE  

connexon – these meet up to form gap junction)

???? 6 protein subunits/connexon

• each subunit is called connexin

▪ gated by pH and intracellular calcium concentration

???? normally open

???? closed by acidity OR high intracellular calcium

▪ bidirectional flow of current

???? rectifying/non-rectifying

???? rapid transmission – anything electrical in  

presynaptic or postsynaptic cell FELT by the other  

(depends on where signal is being generated

▪ tight synchrony – respond instantaneously to what the  

others are doing (because transmission is so quick)

▪ passive signal similar to passive conductance of signal  

within a neuron (except with non-uniform axial  


• 2. chemical synapse: (look at picture on slide)

• chemical transmitters exocytose  

▪ NOT direct transmission of charge

• transduction between electrical ???? chemical ???? electrical

• neurotransmitters go through extracellular space and bind to  postsynaptic cell

▪ OPENS ion channels ???? ions flow in

• postsynaptic receptors

• slower transmission

• function:

▪ presynaptic:

???? AP ???? Ca entry ???? vesicle fusion ???? nt release

▪ postsynaptic:

???? binding of neurotransmitter ???? opening of ion  

channels ???? influx/efflux of ions ???? EPSP or IPSP ????

suprathreshold ???? AP in postsynaptic neuron

???? unidirectional flow of info

• coupling coefficient

• efficiency of which charge transfers

• electrotonic coupling via gap junctions

• coupling coefficient – measure of strength of coupling

• magnitude of response in postsynaptic over that of  


▪ will be value less than 1 (if at 1, perfect coupling –

almost impossible)

• ratio of post response to pre response (B:A)

• function of number of gap junction channels

• more gap junctions = greater coupling effect

• fewer gap junctions = lower coupling effect

• the chemical synapse:

• synaptic cleft

• postsynaptic

• presynaptic

• active zone (nt release)

• chemical synaptic function

• synapses

• axodendritic: stimulate or inhibit action potential generation • upstream from axon hillock

• influences whether or not AP generated at axon

• types:

▪ dendritic shaft – usually inhibitory

???? GABA

???? in more favorable position to influence  

postsynaptic cell because closer to axon hillock

▪ dendritic spine – usually excitatory

???? glutamate

• axosomatic – generally inhibitory

• stimulate or inhibit action potential generation

• upstream from axon hillock

• influences whether or not AP generated at axon

• on soma of postsynaptic cell

• axoaxonic:

• increases or decreases nt release

• mainly at the axon terminal

• INCAPABLE to influence generation of AP in postsynaptic cell • facilitates or depresses nt release

▪ probability of release

???? 1. can increase or decrease by influencing the  

membrane potential

???? 2. influence the synaptic machinery

• chemical synapses

• asymmetric synapses:

• excitatory

▪ glutamate

• bunch of vesicles in presynaptic terminal

• postsynaptic cell has fuzzy dense material under the  


▪ proteins that have become electron dense (PSD-95)

▪ associated with glutamate receptors/synapses in  


• symmetric synapses:

• 2 membrane look the same

• inhibitory


• EPSP: inward current ???? depolarization

• increase in positive charge inside membrane

• IPSP: outward current ???? hyperpolarization

• EPSP + IPSP : inward current + outward current ???? summed response

• presynaptic mechanism of nt release

• experiment: voltage clamp in presynaptic terminal ???? record inward  membrane current

• in presence of TTX (blocks voltage gated sodium channels) ▪ NOT sodium dependent

▪ record postsynaptic change in voltage ???? EPSP

▪ block voltage-gated calcium channels with cadmium

???? this block abolishes EPSP



• calcium influx triggers nt release (exocytosis)

• to get calcium into the cell, we have to activate voltage-gated Ca  channels via depolarization


• AP conducted to terminal ???? membrane depolarization ???? opening of  voltage-gated calcium channels ???? calcium influx ???? nt release • **molecular mechanism of nt release is NOT directly voltage dependent

• calcium dependent process

• voltage-gated calcium channels are responsible for allowing calcium  to enter

• nt release caused by increase in calcium concentration in terminal • exocytosis – nt release (calcium dependent)

• 1. vesicle docking – vesicle and plasma membrane SNARE proteins  associate with one another

• vesicles SNARE: synaptobrevin (in membrane of vesicle) • plasma membrane SNARE: syntaxin (on pm) and SNAP-25 (on pm)

• 2. SNARE complexes form, pulling vesicles close to plasma  membrane (vesicle docking/priming)

• proteins interact in space between vesicle and pm

• 3. calcium entering interacts with vesicle membrane protein  synaptotagamin (Ca sensitive protein)

• ca binds to synaptotagmin (calcium sensor)

• synaptotagamin changes conformation- draws vesicle to pm  and both membranes fuse

• 4. vesicle fusion with membrane

• vesicle folds into membrane, dumps entire  


• another process – kiss and run (pulls back off membrane  instead of folding)

• synaptic vesicle cycle:

• multiple pools of vesicles

• storage pool – not ready for release

▪ connected to actin cytoskeleton to immobilize them in  

presynaptic terminal

▪ mobilized in calcium dependent process to go to readily  releasable pool

• readily releasable

▪ sits next to plasma membrane (docked and ready to  

release when calcium enters)

• synaptic proteins: complex protein-protein interactions in release • anchoring to cytoskeleton

• trafficking to plasma membrane

• docking at membrane

• fusion of vesicular membrane with pm

• formation of fusion pore

• several protein interactions triggered by calcium

• surface area increased with every exocytotic event – needs  something to fix that

• membrane capacitance will increase

• capacitance of membrane is a function of surface area – capacitance increases (more charge on more surface area) • can measure exocytosis by seeing storage of charge

• folding of membrane (for fusion) attracts clathrin proteins to cover  an area of the membrane to designate for endocytosis

• endocytosis: internal budding of vesicles (vesicles coated with clathrin) • compensates for exocytosis (maintains SA of the cell)

• function of exocytosis (more exocytosis ???? more endocytosis) • vesicle membrane subtracted from pm

• dynamin: protein that clips vesicle off after invagination • decrease in surface area

• decrease in capacitance ???? compensatory

• quantal release:

• neurotransmitters released in quanta

• each vesicle is DEFINED QUANTAL UNIT

• quanta: volume of neurotransmitter contained within a vesicle • experiment:

• stimulate motor axon, record endplate potentials (EPP) of  muscle fibers


• motor endplate: axon terminal + muscle fiber  

• spontaneous EPP (no stimulation of axon): miniature  endplate potentials (MEPP)

▪ very small

▪ evoked by single vesicle of neurotransmitters being  


▪ smallest potential possible

▪ unitary event

• evoked EPP amplitudes integral multiples of mini’s

▪ for most, there is a failure to generate an endplate  


???? function of the probability of release (we reduced  

this probability by bathing it in chemicals)

▪ smallest evoked response is about the same size as the  mini EPP

• quantal analysis:

• plotting number of events vs. amplitude of that event

• EPP amplitude histogram:

• number of events at each amplitude – each event is multiple  of smallest event (same size of mini_)

▪ due to nature of nt release (QUANTAL) – defined by  

number of nt in synapse

▪ every vesicle that goes through exocytosis binds to  

about the same number of receptors on postsynaptic  

membrane, opens about the same number of channels,  

causes same amplitude

• polymodal distribution (multiple peaks) – all multiples of  smallest event

• histogram peaks are integral multiples of unitary EPP (mini’s) • release is QUANTAL (discreet units)

▪ 1 quantum = 1 packet of transmitter = 1 vesicle

???? ???? unitary response (miniature postsynaptic  


• same principles in CNS as in motor endplate

• EPSP generation:

• neurotransmitters:

▪ Acetylcholine (NMJ)

▪ glutamate (CNS)

???? triggers inward current ???? EPSP

???? depolarization  

???? receptors are ionotropic

• double channels for K and Na  

• ionic selectivity:

▪ Na+

▪ K+

▪ Ca (only sometimes in CNS)

???? only one subtype

• IPSP generation:

• neurotransmitters:

▪ GABA (most of NS)

???? outward membrane current

▪ glycine (mainly in spinal cord, retina)

• ionic selectivity:

▪ Cl

???? flows in (outward + current)

???? hyperpolarization

• ***No inhibitory junctions in NMJ

Synaptic Transmission II 10/10/15 9:07 AM

• receptors:

• excitatory synapses

o neuromuscular junction

▪ Ach receptors

• central excitatory synapses

▪ glutmate

• inhibitory synapses

• GABA receptors

• chemical synapses – receptors

• 2 types of receptors

o 1. ionotropic: ligand-gated channels

▪ receptor-channel complex

▪ ionotropic – tropic for ions

• 2. metabotropic: 2nd messenger-gated

▪ G-protein-coupled receptors (receptors are NOT  


▪ link up to channels via G

▪ intracellular, downstream signal cascade

???? opens or closes target channel

• types of ion channels

• 1. leak

• 2. ligand-gated (IONOTROPIC)

o domain in extracellular portion of protein that forms pocket – recognizes specific neurotransmitter

▪ causes conformational change in protein to form  


o neurotransmitter-dependent

o ion channel=receptor

• 3. 2nd messenger-gated

• target of metabotropic receptors

• phosphorylation-dependent

• once neurotransmitter binds, causes biochemical cascade

▪ leads to phosphorylation of target protein (channel)

▪ this event causes conformational change in protein ????

opens channel

• 4. voltage-gated

• membrane-potential-dependent

• voltage sensor

• 5. mechanically gated

• sensitive to stretch of membrane

• neurotransmitter receptors

• often have both ionotropic and metabotropic receptors ( • multiple receptor subtypes for each nt

o Ach receptors: endogenous agonist

▪ nicotinic (ionotropic)

???? in neuromuscular junction

▪ muscarinic (metabotropic)

• glutamate receptors

▪ ionotropic

▪ metabotropic

• receptor agonists: activate receptors

• triggers function (ex: opens channel, starts signal cascade) • ex: nicotine (for nicotinic receptors), muscarine (for  

muscarinic receptors)

• receptor antagonists: block receptors

• 2 methods:

▪ bind to ligand binding site on receptor (blocks binding of  nt)

▪ bind to somewhere else on protein to change  

conformation that prevents nt from binding

• ex: crurare (for nicotinic receptors), atropine (for muscarinic) • neuromuscular junction:

• specialized synapse – motor endplate

o muscles made of multiple muscle fibers – each one gets  innervation from motor neuron that makes multiple synapses  from ONE axon

o can have multiple active zones in each synaptic bouton

o nerve-muscle synapse of motor neurons

o axon terminals – synaptic boutons on SAME muscle fiber ▪ area of neurotransmitter release

▪ active zones: synaptic specializations

???? pre and postsynaptic specialization

▪ docking and fusion proteins

▪ mitochondria (energy stores)

▪ synaptic vesicles – Ach (ALL somatic muscles use ACh)

???? ACh is excitatory in all areas

???? ALL nicotinic, ionotropic receptors

???? inward membrane current – influx of positive  


???? depolarizes membrane

▪ calcium channels

• postsynaptic muscle fiber

▪ junctional folds

▪ Ach receptors – at lips of folds

▪ nicotinic receptors

???? ionotropic

• basement membrane (under folds)

▪ acetylcholinesterase

???? Ach breakdown into choline + acetate

???? choline taken back up into presynaptic terminal to  

remake ACh

• motor axon: neural innervation of muscle fibers, 1 axon/fiber • muscle fiber: postsynaptic endplate potentials (EPP)

• miniature EPP – spontaneous release of single vesicles

▪ stochastic - random

• AP – evoked release of multiple vesicles

▪ suprathreshold – causes AP in muscle

▪ muscle contraction

• nicotinic Ach receptors


• requires TWO ACh molecules to bind!!!

• 5 protein subunits – pentamer (heterooentamer bc different  subunits)

o 2α, 1β, 1δ, 1γ subunit

o Ach binding site on α (requires 2 alpha subunits)

▪ 2 Ach molecules required to bind to open channel

• nicotinic ACH receptors

• ligand-gated channel

▪ MIXED cation channel

▪ ligand: ACh

▪ selective for Na AND K

???? both go in opposite directions (Na in, K out)

• due to driving force

???? net INWARD current – Na influx and K efflux

• Na influx dominates K efflux due to  

GREATER driving force

▪ endplate potential (EPP) = EPSP of NMJ (only time we  

call it anything other than EPSP)

• single channel currents

• each time TWO Ach combine

• recorded with patch clamp techniques

o all or none

o inward

• summation of single channel current = whole cell current =  waveform

• EPP (endplate potential) reversal potential

• INa = IK ???? Iin = Iout 

• Vrev for = 0mV

• membrane potential of muscle fiber at which current  zeroes and reverses direction on the other side

• Vm where EPC (endplate current) reverses direction

• when we go above reversal potential: more K out than  sodium in

▪ reverse current direction – outward current

• at resting potential: -120 mv driving force on sodium, 10 on K ▪ more on Na

• move membrane potential from resting to -30mV

▪ activate synapse

▪ driving force of -90 mV on sodium, 50 mV on K

???? Na still dominates, but getting closer

???? SMALLER inward current (more potassium going  

out relative to sodium going in than previous  


• move membrane potential to 0 mV

▪ driving force -60mV on Na, 80 mV on K

???? K driving force dominates – larger OUTWARD  


• takes a little more driving force on K because Na can go  through channels easier (higher permeability in channel)

• single channel current parallel whole-cell currents, except they’re  square (all or none)

• membrane will be polarized in direction of the current

• inward - add positive charge inside – EPP that is excitatory  (depolarizes)

• outward –positive charge goes out – EPP that is inhibitory  (hyperpolarizes)

• look at picture on slide! (EPP reversal potential)

• whole cell currents produce endplate potentials

• current flow direction and amplitude sum of constituent ionic  currents, which is a function of the driving force on each ion • video:

• ionotropic glutamate receptors (excitatory)

• when glutamate binds, these receptors open channel

• different proteins

• 3 receptors:

• *AMPA (AMPA required to bind, then AMPA channel opens) • *Kainate


• AMPA and Kainate

• mixed cation channel that fluxes sodium and potassium • same efficiency as nicotinic receptors (same ions)

• when glutamate binds, sodium flows in, potassium flows out ▪ because sodium dominates in terms of driving force

• permeable to Na and K

• similar to ACh, nicotinic receptors

• purely ligand-sensitive

• EPSP/EPSC reversal

• if both ions flux with equal efficiency, reversal potential is halfways  between two equilibrium potentials

• for these it is -10 (sodium is slightly better at coming in than  potassium is at going out)

• reversal potential of AMPA and Kainate is 0 mV

• current through these receptors almost identical to current  through nicotinic and cholinergic receptors

• recruitment of afferent axons

• increasing stimulus intensity

• increasing EPSP amplitude

• neurotransmitter = glutamate

• receptors = AMPA receptors

• reversal potential

• mixed Na/K current

• Vreversal = 0mV

• similar to ACh nicotinic R

• NMDA receptors (ionotropic glutamate receptor)

• Na/K AND Ca permeable

• Ca will flow inward through NMDA

• ligand-gated AND voltage sensitive

• Mg2+ block leads to voltage-sensitivity

• Mg binding in site within pore

• depolarizes induces unblock

• when resting potential – magnesium clogs pore (EVEN if glutamate  has binded)

• to get ion flux through channel, membrane needs to be  DEPOLARIZED to remove magnesium block (weakens negative  charge inside)

• more depolarized ???? less magnesium

• occurs around -40—50 mV

• once Mg leaves binding site, both Ca and Na in (combination acts  like Na alone in AMPA receptor), K out

• mixed current reversal potential of 0mV

• requires co-agonist (based on subunit composition)

• ONLY NMDA receptor needs this

▪ some need glycine, some need serine

▪ CRITICAL for activation – without it glutamate binding  does not open channel

???? requires TWO ligands at different sites to open  


• other modulatory sites

• glycine or serine– co-agonist

▪ provided by glia

▪ plenty floating around – always available

• Zn – antagonist

• PCP – antagonist

• mixed AMPA/NMDA

• mixed population of postsynaptic receptors (NMDA and AMPA) • under normal conditions, glutamate released and binding to NMDA  and AMPA

• because Mg block, only AMPA receptors flux ions and mediate  inward membrane current (in baseline conditions)???? EPSP • backpropagating action potentials have a huge role – depolarizing  dendrites to kick Mg out of NMDA receptors

• permanent changes in terms of plasticity

• long term potentiation works at glutamate synapse

• synaptic plasticity (changing postsynaptic signals) triggered  by calcium influx through NMDA receptors

• AMPA/NMDA current

• generate current voltage relationship

• Na, K and Ca channels

• NMDA will only come online when depolarized

• mixed glutamate receptors


▪ NMDA receptor antagonist (blocks only NMDA)

▪ blocks NMDA current

• NMDA current

▪ slow component

???? takes longer than AMPA

???? doesn’t open until few seconds after initiation of  


???? slow offset though – lasts longer

▪ slower than AMPA (activated immediately)

???? also very rapid offset

• hyperpolarized potential:

• activate AP synapse ???? EPSP

• inward current

• when stimulated 2nd time with APV – little to no change in  synaptic current (because NMDA was already blocked and  there is no ion flux)

• because only AMPA, high current lasts longer

• depolarized to -40

• activate AP synapse ???? EPSP

• response duration changes upon addition of APV (because at - 40 mV the NMDA was going to influence the EPSP)

▪ due to APV, NMDA  

• much larger NMDA receptor component

• yellow portion on graph is solely due to NMDA

• voltage sensitivity

• NMDA current at depolarized membrane potentials only

• Mg block

▪ blocks channel at hyperpolarized potentials ???? 0 current,  0 change in voltage

▪ channel unblocked at depolarized potentials (threshold

around -60 mV)

▪ voltage sensitivity of NMDA current abolished with 0 Mg • current-voltage relationships

▪ non-linear with Mg, linear without Mg

• current through Kainic and AMPA receptors doesn’t change with voltage,  whereas current for NMDA gets bigger with depolarization

• NMDA curve NOT linear

• GABAA receptors

• heteropentamer

• α, β, δ, γ, p subunits

• Cl- channel

• modulatory sites

▪ 1. GABA – ligand

▪ 2. barbiturate – agonist

▪ 3. benzodiazepine – agonist

▪ 4. steroid – agonist

▪ 5. picrotoxin – antagonist

▪ 6. ethanol – agonist

• outward current – composed of outward single channel currents • IPSP reversal

• inhibitory interneuron

• neurotransmitter

▪ =GABA (CNS and spinal cord)

▪ =glucine (only spinal cord)

• receptors

▪ GABA ???? GABAA receptors

▪ glycine ???? glycine receptors

• outward current at rest

▪ Vreversal = -70 mV

• Cl- current

• shunting inhibition

• shunting of current out of cell via open Cl- channels • Ohm’s law V= IR

10/10/15 9:07 AM

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