Neuronal Biophysics Flashcards

0
Q

Ohm’s Law:

1) I = ?
2) G = ?
3) I = ?

A

I=GV
G= 1/R
I= V/R

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1
Q

What describes the relationships between current (I), voltage (V), conductance (G) and resistance (R)?

A

Ohms law

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2
Q

According to ohm’s law if voltage increases what happens to current?

What if resistance increases?

A

Current increases

Current decreases

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3
Q

What is the Nernst equation?

What is the simplified version at 37*C?

A

Ex = RT/zF ln [x]o/[x]i

Ex = 61.5 log [x]o/[x]i

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4
Q

What are the extracellular and intracellular concentrations of Cl-?

A

Ex 123mM

In 4.2 mM

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5
Q

Remember that valency and charge affect the Nernst eq. What are the equations for Ca2+ and Cl-?

A

Eca = RT/2F ln [X]o/[X]i

Ecl = RT/F ln [X]i/[X]o

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6
Q

What happens to the ratio of extracellular to intracellular ion conc in the Nernst eq if the ion is negatively charged?

A

Inverted

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7
Q

What eq shows contribution of different ions to resting potential?

A

Goldman-Hodgkin-Katz

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8
Q

If membrane permeable to Na and K what’s is the GHK eq at 37*C?

A

Vm = 61.5log (Pk[k]o + Pna[na]o)/(Pk[k]i + Pna[na]i)

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9
Q

What creates an asymmetric distribution of ions across the membrane?

A

Integral membrane proteins: Ion channels, pumps and transporters

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10
Q

What is an important feature of an ion channel?

A

Selective permeability

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11
Q

What’s different between the movement of ions through ions channels and transporters compared to pumps?

A

Channels/transporters move ions down electrochemical grad

Pumps move ions AGAINST electrochemical grad

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12
Q

What part of a VG ion channel contains the selectivity filter?

A

Pore

Structure of pore determines which ions pass

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13
Q

VG ion channels have a gate which controls the pore but what controls the gate?

A

Voltage sensor

Movement of sensor causes conformational changes in channel protein cause gate to open

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14
Q

Describe the structure of a VG ion channel

A

4 identical subunits/domains

Each domain contains 6 transmembrane alpha helices (s1-s6. S4 is voltage sensing)

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15
Q

How does the K+ selectivity filter work?

A

Interactions between K+ and waters if hydration replaced by interactions with O2 atoms lining pore that bind K+

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16
Q

Why can’t Na+ pass K+ selectivity filter?

A

Too small

Can’t contact O2 atoms on both side of filter, not thermodynamically efficient to remove waters of hydration

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17
Q

How do Na channel gates work? (Activation and inactivation gates)

A
Activation gate (m) opens upon depolarization 
Inactivation gate (h) blocks pore 5ms after depolarization
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18
Q

How do Na channel gates contribute to refractory period?

A
Inactivation gate (h) remains blocking pore for a short time after depolarization 
Further Na influx not possible
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19
Q

What is mainly responsible for setting resting Vm?

What else contributes?

A

Background K+ activity

Na+ and K+ ATPase

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20
Q

Activation of which channels depolarise the membrane and is therefore excitatory?

A

Na+
Ca2+
Non selective cation channels

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21
Q

Activation of which channels hyperpolarize membrane and are inhibitory?

A

K+

Cl-

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22
Q

What are the Nernst potential for: K, Na, Ca, non-selective cation and Cl-?

A
Ek= -90mv
Ena= +65 mv
Eca = +110 mv
Ecat = 0 mv
Ecl= varies, in adult CNS usually -90mv
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23
Q

What is the equation for driving force of an ion?

A

Driving force = Vm - Eion

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24
Q

What direction of flow has a positive ionic driving force?

A

Outward

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25
Q

What direction of flow has a negative ionic driving force?

A

Inward

26
Q

What is a reversal potential?

A

Vm at which direction of current flow reverses

27
Q

If only K+ channels open what is the reversal potential?

Why in reality is Erev never exactly Eion?

A

= Ek = -90mv (zero current at -90)

Membrane never 100% selective for one ion, always leaks

28
Q

What is voltage-clamp recording?

What’s it used for?

A

Voltage controlled, current measures

Used to test properties of ion channels, esp VG channels

29
Q

What’s current-clamp recording?

What’s it use for?

A

Current controlled, voltage response recorded

Mimics APs and synaptic input

30
Q

What deflection is an outward current?

A

Upward

31
Q

What deflection in an inward current?

A

Downward

32
Q

Calcium-activated K+ channels which phases of AP and why?

A

Repolarization. Activated by actuation of VG Ca channels

Afterpolarization - open longer than VG k+ channels, slow repolarization

33
Q

Why is AP unidirectional?

A

Refractory period

Na channels inactivated behind depolarization

34
Q

Why is there a high conc of VG channels at nodes of Ranvier?

A

Saltatory conduction in myelinated axons

35
Q

What determines firing properties of neurones?

A

Ion channel expression profile

36
Q

What technique allows the characterisation of ion channels and their contribution to firing patterns?

A

Patch-clamp

37
Q

Describe the general principle of patch-clamp

A

Pipette (containing electrolyte solution) placed on cell membrane. Suction applied to create high-resistance gigaohm seal.
Ions fluxing through channels in membrane flow into pipette

38
Q

What does on-cell/cell-attached patch clamp allow?

A

Recording trough single ion channel without disrupting cell interior

39
Q

Explain whole-cell recording

A

Cell membrane ruptured and cytoplasm continuous with pipette

Use to record current from entire cell (voltage clamp a whole cell)

40
Q

Explain inside-out patch clamp

A

Pipette retracted in on-cell configuration to excuse patch of membrane
Cytosolic membrane surface exposed

Used to study single channel activity

41
Q

Explain outside-out patch clamp

A

Pipette retracted from whole cell configuration to break off patch of membrane
Extracellular surface exposed

Used to study effects if extracellular cues like NTs

42
Q

What type of recording shows gating properties of channels?

A

Whole cell

43
Q

What is the threshold for VG Na and Kv activation?

A

VG Na - -50mv

Kv - -20mv

44
Q

When are outwardly rectifying k+ channels open?

A

Permeable to K+ when Vm > Ek (more positive than Ek)

Open at depolarization

45
Q

When are inwardly rectifying k+ channels open?

A

Hyper polarization

At Vm < Ek (more negative than Ek)

46
Q

When is the pore of inwardly rectifying K+ channels blocked? And what is it blocked by?

A

Positive potentials (>Ek)

Intracellular substance like Mg2+ and polyamines

47
Q

Which current is inactivating?

A

A current (Ia)

48
Q

Which current is non-inactivating?

A

M current

49
Q

H current is conducted through what type of channels?

A

Hyperpolarisation activated, cyclic nucleotide gated (non-selective) cation channels (HCN channels)

50
Q

GIRK channels are a type of what kind of K+ channel?

A

Inward rectifier

51
Q

What channels are large-conductance also called BK channels?

A

Ca-dependent k channels

52
Q

What effect does M current have on AP firing?

So what is the effect of inhibiting M current?

A

Acts as brake on AP firing, inhibits firing

Increased firing, excitation

53
Q

What inhibits M current?

A

Muscarinic Ach receptor (M1)

  • activates Gq -> PLC
  • PKC and Ca inhibit M channel

(This excites sympathetic neurones)

54
Q

How does Muscarinic Ach receptor inhibit cardiac muscle?

A

M2 receptor activates GIRK channel via Gi activation

55
Q

What current contributes to background/leak K+ conductance?

A

M current

56
Q

Other than VG Na and K channels what 4 other channels contribute to rhythmic activity of neurone?

A
VG Ca channels
Ca-dependent K channels
HCN channels (hyperpolarisation activated cation channels - Ih)
T-type Ca channels
57
Q

What is the role of VG Ca channels?

A

Increase [Ca]i

58
Q

What is the role of Ca-dependent k channels?

A

Long lasting afterhyperpolarisation

59
Q

What is the role of HCN channels?

A

Depolarization (and stop repolarization )

60
Q

What is the role of T-type Ca channels?

A

Cause burst of AP firing

61
Q

Does a mature neurone have low or high intracellular Cl-?

What type of channels does it express more?

A

Low

Outwardly directed channels - KCC2

62
Q

Does an immature neurone have low or high intracellular Cl-?

What type of channels does it express more?

A

High

Inwardly directed channels - NKCC1