Sodium Revision Flashcards

1
Q

First evidence that TTX was a NaV specific blocker

A

Sucrose Gap - Voltage clamp of lobster giant axons
94nM

no effect on K+ current

Narahashi, Moore and Scott, 1964

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Structural determination

A

Tsuda 1964

Guanine

+ one positive charge at physiological pH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

External block

A

TTX block outside nerve membrane

Blocking action devoid on internal perfusion

Narahashi, Anderson and Moore, 1967

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Support of cationic block

A

Hille, 1975

Permeability titrates away at increasingly low pH owing to the presence of protons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

TTX block in relation to gating

A

Keynes and Rojas, 1974

Measured gating currents of Nav not affected by TTX

Plugging blocks flow from outside even though gating mechanism normally operates upon depolarizing stimulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

One-to-one stochiometric block suggests

A

Q, Y + N, 1985

Characteristic of single ion channel not affected

Observation open decreases dose-dependently

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Relative sizes of subunits

A

250

33-37

kDA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Hairpin P loop

A

S5-S6 of DIII

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

TTX binding sites

A

All S5-S6 of domains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

u-Connotoxin binding site

A

Only S5-S6 of DII

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

NT binding site 2

A

S6 of DI and DiV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

NT binding site 3

A

S3-S4 linker DIV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

NT binding site 4

A

S1-2 linker DII

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

NT binding site 5

A

S6 DI and S5 DIV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Beta subunit important for

A
Voltage dependency 
gating
cell adhesion
signal transduction
expression at PM
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

IFMT is where

A

Between DIII and DIV

17
Q

S4 time course associates with

A

onset of inactivation or slow ON gating charge

18
Q

Why is S4 not inactivating particle?

A

Goldshem-Ohm 2013 - inactivation deficient mutant -> movement leads to secondary conformational change exposes binding site for inactivating particle

19
Q

Docking site consists of

A

S4-S5 DIII and DIV

CTD S6 DIV

20
Q

Binding site has what type of residues?

A

Miyamoto 2001 - hydrophobic - allows phenyalanine at P1489 to interact with alanine in DIII S4-S5 and asparaganine DIV S4-S5

21
Q

What does hair-pin structure do?

A

Sirota 2002 - optimizes interaction etween IFMT and docking site - outtward movement occurs around a hinge comprised of glycine and proline

22
Q

What might underlie slow inactication

A

Capes 2013 - disable DIV S4 -> by introducing glutamine in the first 3 charge carrying residues -> slow entry and recovery from fast inactivated states

23
Q

CNS Nav’s are

A

Nav1.3 fetal nervous system tissue

1.1 , 1.2 and 1.6 in adults

24
Q

Where are 1.1 and 1.3 expressed and what does this indicate?

A

Soma of CNS neurons -> integrate synaptic impulses -> set AP initiaition and propagation to dendritic and axonal compartments

25
Nav1.2
expressed in unmyelination neurons - conducts AP - westenbroek 1989
26
Nav1.6
expressed in nodes of Ranvier in developing neurons - saltatory conduction - Boiko 2001
27
How many alpha subunits?
Yu and Catterall 2003 - 10 distinct pore-forming alpha subunits, 9 of which are functional
28
Nav1 contributes to
upstroke of AP
29
Nav1.4
skeletal respiratory muscle ECC
30
SCN4A mutants lead to
altered skeletal muscle excitability - periodic paralysis - congenital myopathy - myasthenic syndrome
31
Cardiac current needs
rapid depolarization
32
Nav1.5 provides
fast, subsequent opening - ECC re-open in plateau phase - late inward / persistent current -> viophysical proeprties of cardiac current
33
Where else is 1.1 + 1.6 expressed
in adult PNS
34
What is more expressed in PNS how was this found?
1.7, 1.8 and 1.9 -? cloned from sympathetic and DRG neurons