Lecture 4: Neural Communication 1 Flashcards

1
Q

The synapse

A

• Site of neural communication: between axon terminal and dendrites of another neuron

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2
Q

Resting Membrane Potential

A

A healthy neuron has a resting membrane potential (or membrane voltage) of between -60 and -80 mV (the voltage inside the neuron is 60-80 mV less than outside the neuron). usually -65mV

  • Sticking a needle inside a cell (intracellular electrode), then stick a needle outside the cell (extracellular electrode), & compare the charges (potential energy)
  • potential is always a comparison between 2 sides: inside and outside of the cell
  • inside is slightly negative compared to the outside of the cell
  • mV = millivolts
  • right along the membrane* ionic changes/voltage differences
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3
Q

The membrane potential … originally performed with invertebrates

A

o On average can have very large neurons, as compared to humans

o The solution of myelin (fatty sheathes that wrap around the axon), is only seen in vertebrate animals (have spinal cord)

o Their solution: built really big axons, more efficient conduction of the action potential

o In some, their neurons/axons are much bigger/easier to study

o how big? about 1mm in diameter - can drop an electrode directly in there

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4
Q

Neuronal communication is chemical

A

1) primarily the result of two ions, sodium (Na+) and potassium (K+)
2) ions move into or out of the cells, but not freely

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5
Q

Neuronal communication is electrical

A

1) ions are positively and negatively charged (Na+ and K+ are both positive - missing an electron)

2) as they move into or out of cell, they change the potential (voltage) at the membrane
o note: absence of pos. is neg.
o i.e. remove a pos., leave a neg.

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6
Q

Chemical gradients

A
  • Ions want to flow from high concentration to low concentration
  • Chemical force, actual thing pushing on these ions

• Swimming pool:
o down at the corner there is this bubble, where you’re supposed to enter the pool… the stairs
o separate that area will a wall, and put dye into the entrance/stairs portion
o remove the wall, what happens to the dye?
 move out from that little area into the rest of the pool
 spread out equally; in all directions

• lots and lots of ions inside cell: chemical force pushing them to the outside & vice versa

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7
Q

Electrical gradients

A
  • Charge/potential wants to flow from high concentration to low concentration, too
  • Sometimes electrical and chemical gradients are at odds, causing an equilibrium that =/= 0mV
  • Cells are resting at a negative; positive ions want to move into the cell
  • Sometimes they will be pushing on the same ions, in different directions (electrical and gradient)
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8
Q

The cell membrane - guardian

A

• lipid bilayer is tightly packed, both hydrophobic and hydrophilic, keeping out all dangerous entities

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9
Q

o phospholipid bilayer

A

 “head” — hydrophilic (inside and outside the cell)
- happy to interact with molecules similar to water (polar), anything non-polar/fatty (like oil) will bounce off these heads

 “tails” — hydrophobic (pointing inward towards each other)

      - lipid tails; fatty
      - don’t like to interact with water; will bounce off the tails
      - will interact with fatty-like/non-polar things

 Effective barrier: keeps almost everything out
- Foreign invading bodies; viruses

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10
Q

Channels and pumps

A

• only certain molecules and ions permitted via channels and pumps

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11
Q

channels

A

o allow PASSIVE diffusion (i.e. along chemical gradient)
 proteins that cause a pore (hole); allow a passageway from one side to the other
 don’t allow just any ions; only certain ones
 when they open; ions are going to move according to the law of nature (e.g. lot on the outside, going to want to move to the inside)
 useful, limited in the directions that the ions will move “forces of nature”

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12
Q

Pumps

A

o actively push ions against their chemical gradient
 requires energy (ATP - adenosine triphosphate)
 not just a hole; “double-door” — allow things to travel
 things come into a little out-cove, from there the outer door closes, then the inner door opens and the ions can move in
 will actively pump ions against their concentration gradients; mechanistic action; require ATP

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13
Q

A cell with no pumps or channels

A
  • nothing moves in or out of the cell
  • draw in a phospholipid bilayer
  • roughly the same amount of Na+ and K+ — concentration is the same
  • even if tore a hole, concentration would remain the same
  • no chemical gradients, no electrical forces
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14
Q

The sodium-potassium pump

A
  • active process —requires ATP; mechanistic action; can push against concentration gradients (much slower than a channel)
  • embedded in cell membrane

• extremely important
o consumers 2/3 of all neuronal energy

• pushes/pumps 3 Na+ out, and 2 K+ in ***
o i.e. active process that requires energy

• how does this affect the chemical gradients?
o more Na+ (sodium) on the outside, means pushing from the outside to the inside
o pumping more K+ (potassium) inside; building up the concentration inside… higher concentration inside — chemical gradient pushing from the inside to the outside

• how does this affect the electrical gradients?
o leaving the inside charge with a -1 with each pump… building up a chemical gradient (with respect to the outside)
o leaving the inside slightly negative compared to the outside

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15
Q

Potassium “leak” channels

A
  • K+ can move freely via K+ “leak” channels that are always open
  • Na+ cannot move freely across the membrane: it has channels, but they are usually closed (resting conditions)
  • (Chemical gradient strong; from the inside to the outside — as K+ is leaving, making the inside more negative (building up the gradient) to push them back into the cell)
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16
Q

Cells are POLARIZED

A

• Na+/K+ pump pushing more Na+ out of the cell than K+ into cell
o Result: inside out of cell slightly more negative, than outside

• But, K+ can move freely through its leak channels
o Result: K+ wants to move with chemical ingredient, out of the cell

• But, this moving K+ is making the cell even more negative
o Result: flow of K+ stops, when force of electrical gradient equals force of chemical gradient

• End result: cell has resting membrane potential of roughly -70mV (equilibrium

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17
Q

When a neurotransmitter molecule binds to a postsynaptic receptor, it can have one of two localized effects (1)

A
  1. depolarize the membrane
    o e.g. decrease the membrane potential from -70 to -67mV
    o Move towards zero (more positive)
  2. hyper-polarize the membrane
    o e.g. increase the membrane potential from -70 to -72mV
    o move farther from zero (more negative)
18
Q

When a neurotransmitter molecule binds to a postsynaptic receptor, it can have one of two localized effects (2)

A

1) depolarize the membrane = excitatory postsynaptic potential (EPSP)
o potential: comparing the inside of the cell to the outside, using electrode
o postsynaptic: measure on the postsynaptic membrane (dendrites)
o excitatory: getting the cell ready to fire an action potential

2) hyper-polarize the membrane = inhibitory postsynaptic potential (IPSP)
o inhibitory: moving away from action potential

19
Q

When a neurotransmitter binds to a postsynaptic receptor, it can have one of two localized effects (3)

A

i. depolarize the membrane = EPSP = increase in likelihood that the postsynaptic neuron will fire and action potential (AP)
ii. hyperpolarize the membrane = IPSP = decrease the likelihood that the postsynaptic neuron with fire an AP

20
Q

• the transmission of postsynaptic potentials (PSPs) is….?

A

graded, rapid, and decremental: PSPs travel like an electrical signal along an uninsulated wire

o graded:
 a stronger signal would cause bigger EPSPs

o rapid:
 when the voltage inside the membrane changes (EPSP), that will spread along the membrane at the speed of light (virtually instantaneously)

o decremental:
 as its spreading out, much like lightning/striking a pond: electricity spreading throughout the pond (fish on the top die, those on the bottom may live)… as it spreads, sort of decays
 as it spreads further from the receptor, it decays more and more

21
Q

EPSPs and IPSPs sum both …?

A

spatially and temporally

  • EPSPs small: many need to all sum up onto of one another, in order to reach the firing of an action potential
  • Can sum up over space and time = always a combination
22
Q

Spatially:

A

o 2 excitatory synapses; 2 inhibitory synapses
o 2 different EPSP simultaneously sum to produce a greater EPSP
o 2 simultaneous IPSPs sum to greater IPSP
o A simultaneous EPSP and IPSP cancel each other out

23
Q

Temporally

A

o 2 EPSPs in rapid succession synergize (stack-up) to produce a larger EPSP
o 2 IPSPs in rapid succession synergize to produce a large IPSP

24
Q

AP generation

A
  • if the sum of the EPSPs and the IPSPs that reaches the axon initial segment is sufficient to depolarize the membrane there above its threshold of excitation (e.g., -55mV) then an action potential (AP) is generated
  • the AP is a massive momentary reversal of the membrane potential (e.g. from -70 to +55mV)
25
Q

Reverse the polarity

A
  • action potential: a rapid, brief reversal of the polarity at the membrane, from negative to positive
  • it’s the main method of brain communication

• it’s all or non (off or on), not graded (e.g. 1-100%)
o i.e. always the same size/shape in cell
 cannot convey strength/magnitude on the action potential
o how do neurons convey magnitude, then?
 Through hyperpolarization and depolarization - the PSPs

26
Q

Why does this reversal happen? (Reverse polarity)

A

i. depolarization (rising) phase
o from zero-action potential = polarization
o Na+ channels

ii. repolarization phase
o traveling back down to resting potential
o K+ channels open (voltage-gated and leak)

iii. hyperpolarization phase
o slight period
o voltage-gate K+ channels, slow to close, little hyperpolarization phase — more K+ on the outside (pumps trying to maintain the equilibrium)

27
Q

Once the membrane potential reaches a certain threshold,…?

A

an action potential (AP) can be generated

28
Q

AP generation and conduction are both the result of voltage-activated ion channels (primarily Nav)

A
  • lots of channels; while resting are closed
  • when the voltage reaches a certain threshold; the channels change shape, into a different conformation — they open, Na+ can flow through them
29
Q

Small depolarizations

A

• remember: Na+ channels usually closed
o but, these Na+ channels are voltage-gated meaning they open at a certain voltage (ex. roughly -55mV)

• when enough EPSPs arrive at the same time (roughly 5-10mV), the membrane is depolarized enough to reach the Na+ channels’ voltage threshold (threshold potential), and the channels open!

• which direction does Na+ want to flow? why?
o chemical force/gradient
 more Na+ outside of the neuron;
 chemical gradient pushing Na+ from the outside to the inside

o electrical force/gradient
 at rest; the inside of the cell is negative, with respect to the outside of the cell
 positive things will want to move into the cell, towards the negative space
 the electrical gradient are also pushing Na+ into the cell

o together: a very strong force, pushing Na+ into the cell — overwhelms the other ionic forces at that moment

30
Q

Rapid huge depolarizations

A

• Na+ channels open → Na+ into cell
o Effect?
 Positive ions coming into the cell; cell is going to be more positive — depolarize

• Cell membrane flips from neg. to positive

• BUT Na+ channels have built-in inactivation (state 3)
o Shut-off automatically, after roughly 1ms - plug the sodium channel, can no longer flow (why we have our peak/action potential stops)

• Na+ channels stay inactivated until membrane goes back to resting membrane potential
o i.e. no more action potentials until reset!
o repolarization phase
o this leads to the ABSOLUTE refractory period… you cannot have another action potential

31
Q

Repolarization

A

• K+ channels, as always, are open

• But even more K+ channels open during AP (some others are voltage-gated)… K+ channels slow to open, open at AP begin to open after Na+ channels open.
o More K+ on the inside of the cell; chemical gradient pushing K+ from the inside to the outside
o Electrical gradient, at the peak of the AP, the membrane is now positive

• Membrane is now pos., so which way does K+ flow?
o Potassium wants to move outside the cell (electrical force), leaving a negative behind
o Effect: return cell to neg. resting membrane potential

  • Slow closing of voltage-gated K+ channels leads to hyperpolarization phase and the relative refractory period - need more EPSPs to elicit an AP, is possible, takes more than usually
  • Na+/K+ pump restores ion balance over time (slow) - playing no role in the action potential
32
Q

Effect of sub-threshold stimulation of an axon:

A
  • An excitatory potential is produced, but it is not sufficient to elicit an AP
  • Spread down the axon, but decay; not strong enough to reach the axon terminals
33
Q

Effect of supra-threshold stimulation of an axon:

A
  • An excitatory potential is produced that exceeds the threshold of excitation and produces an AP that continues undiminished down the axon
  • No matter where you measure on the axon, the AP has not decayed — non-decremental (constantly regenerated)
34
Q

Conduction in an unmyelinated axon

A

• Na+ (voltage gated) channels are present all along the axon
o Can cause an AP; will spread; will cause another Na+ channel to open, cause an AP, will spread - regenerated
o Keep going down the axon: opening different channels, kind-of spaced out (although pretty close together, so that it travels all the way to the end)

• Unmyelinated axons: Na+ channels everywhere
o Cumulatively speaking, the number of channels will change the speed — actually slows down the action potential quite a bit (the more you have, the slower)
o Solution: myelin « build a bigger wire »

35
Q

Axon Myelination

A
  • produced by glia
  • act as insulation; as charge is traveling down the axon, it decays much less quickly
  • Nodes de Ranvier: unmyelinated axon
36
Q

Conduction in a Myelinated Axon

A
  • Na+ channels are present all along the axon
  • Unmyelinated axons: Na+ channels everywhere

• Myelinated axons: Na+ channels only at the Nodes de Ranvier
o Speeds up connection; fewer channels open
o The voltage is spreading much more in its passive form, in the speed of light

37
Q

Speed and direction

A

• Action potential is faster down myelinated axon than unmyelinated axon
o why?
1) you are opening fewer doors; voltage gated sodium channels
2) the AP is spending more time traveling passively under the myelin
• Action potential only travels in one direction
o Thanks to Na+ channel - why?
 Inactivation gate: absolute refractory period

38
Q

End of the line

A
  • Axon ends in terminal boutons
  • Bouton has vesicles (“bubbles”?) [made of the phospholipid bilayer] filled with neurotransmitters — high concentration

• Action potential depolarizes bouton
o Causes voltage-gated Ca++ channels to open
o Ca++ causes vesicles to fuse with membrane
o Neurotransmitters release into synapse
o Bind to receptors of the postsynaptic receptor (dendrite)

39
Q

Welcome to the synapse

A

• Dendrite membrane has special receptors that fit, like lock and key, with the neurotransmitters

• Receptors are often just (closed) channels that open when they bind with neurotransmitter!
o i.e. ligand-gated ion channels
 receptors will open up, and ions will flow
 little less specific

40
Q

Types of potentials

A

PSPs APs

Graded Yes No

Strength AM
(amplitude modulated) FM
(frequency modulated;
more AP/sec)

Rapid Yes Less so
Decremental Yes No