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Flashcards in Neuronal Biophysics Deck (63):
0

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

Ohms law

1

Ohm's Law:
1) I = ?
2) G = ?
3) I = ?

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

2

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

What if resistance increases?

Current increases

Current decreases

3

What is the Nernst equation?

What is the simplified version at 37*C?

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

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

4

What are the extracellular and intracellular concentrations of Cl-?

Ex 123mM
In 4.2 mM

5

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

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

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

6

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

Inverted

7

What eq shows contribution of different ions to resting potential?

Goldman-Hodgkin-Katz

8

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

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

9

What creates an asymmetric distribution of ions across the membrane?

Integral membrane proteins: Ion channels, pumps and transporters

10

What is an important feature of an ion channel?

Selective permeability

11

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

Channels/transporters move ions down electrochemical grad

Pumps move ions AGAINST electrochemical grad

12

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

Pore

Structure of pore determines which ions pass

13

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

Voltage sensor

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

14

Describe the structure of a VG ion channel

4 identical subunits/domains
Each domain contains 6 transmembrane alpha helices (s1-s6. S4 is voltage sensing)

15

How does the K+ selectivity filter work?

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

16

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

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

17

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

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

18

How do Na channel gates contribute to refractory period?

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

19

What is mainly responsible for setting resting Vm?

What else contributes?

Background K+ activity

Na+ and K+ ATPase

20

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

Na+
Ca2+
Non selective cation channels

21

Activation of which channels hyperpolarize membrane and are inhibitory?

K+
Cl-

22

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

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

23

What is the equation for driving force of an ion?

Driving force = Vm - Eion

24

What direction of flow has a positive ionic driving force?

Outward

25

What direction of flow has a negative ionic driving force?

Inward

26

What is a reversal potential?

Vm at which direction of current flow reverses

27

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

Why in reality is Erev never exactly Eion?

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

Membrane never 100% selective for one ion, always leaks

28

What is voltage-clamp recording?

What's it used for?

Voltage controlled, current measures

Used to test properties of ion channels, esp VG channels

29

What's current-clamp recording?

What's it use for?

Current controlled, voltage response recorded

Mimics APs and synaptic input

30

What deflection is an outward current?

Upward

31

What deflection in an inward current?

Downward

32

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

Repolarization. Activated by actuation of VG Ca channels

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

33

Why is AP unidirectional?

Refractory period

Na channels inactivated behind depolarization

34

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

Saltatory conduction in myelinated axons

35

What determines firing properties of neurones?

Ion channel expression profile

36

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

Patch-clamp

37

Describe the general principle of patch-clamp

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

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

Recording trough single ion channel without disrupting cell interior

39

Explain whole-cell recording

Cell membrane ruptured and cytoplasm continuous with pipette

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

40

Explain inside-out patch clamp

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

Used to study single channel activity

41

Explain outside-out patch clamp

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

What type of recording shows gating properties of channels?

Whole cell

43

What is the threshold for VG Na and Kv activation?

VG Na - -50mv

Kv - -20mv

44

When are outwardly rectifying k+ channels open?

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

Open at depolarization

45

When are inwardly rectifying k+ channels open?

Hyper polarization
At Vm < Ek (more negative than Ek)

46

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

Positive potentials (>Ek)

Intracellular substance like Mg2+ and polyamines

47

Which current is inactivating?

A current (Ia)

48

Which current is non-inactivating?

M current

49

H current is conducted through what type of channels?

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

50

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

Inward rectifier

51

What channels are large-conductance also called BK channels?

Ca-dependent k channels

52

What effect does M current have on AP firing?

So what is the effect of inhibiting M current?

Acts as brake on AP firing, inhibits firing

Increased firing, excitation

53

What inhibits M current?

Muscarinic Ach receptor (M1)
- activates Gq -> PLC
- PKC and Ca inhibit M channel

(This excites sympathetic neurones)

54

How does Muscarinic Ach receptor inhibit cardiac muscle?

M2 receptor activates GIRK channel via Gi activation

55

What current contributes to background/leak K+ conductance?

M current

56

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

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

57

What is the role of VG Ca channels?

Increase [Ca]i

58

What is the role of Ca-dependent k channels?

Long lasting afterhyperpolarisation

59

What is the role of HCN channels?

Depolarization (and stop repolarization )

60

What is the role of T-type Ca channels?

Cause burst of AP firing

61

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

What type of channels does it express more?

Low

Outwardly directed channels - KCC2

62

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

What type of channels does it express more?

High

Inwardly directed channels - NKCC1