Role Of Kv1 And Kv3 In Neuronal Excitability

Question 1

Where can kv2.2 channels be found?

Answer 1

Heart and brain
Kv2.1 = neocortex/ hippocampus
Kv2.2 = medial nucleus of the trapezoid body

Question 2

What happens on kv1 Blockage by dendrotoxin?

Answer 2

For a stimulus which would normally produce a single AP, multiple action potentials will fire.
No increase in threshold

Question 3

What is the function of kv channels in the brainstem?

Answer 3

Involved in sound localisation

Question 4

What two factors contribute to sound localisation and where do they input to?

Answer 4

Time difference - ear closest to sound will receive sound first. Transmits to ipsilateral and contralateral Medial superior olive

Volume difference - ipsilateral lateral superior olive closest to sound is excited by noise. It is then inhibited by glycinergic inputs from the ipsilateral MNTB Which receives inputs from the contralateral cochlear nucleus which is excited by the same sound by at a lower volume.
Integration of the same sound with differences in volume. The LSO will compute differences in firing rates

Question 5

At what voltage do kv1 channels active?

Answer 5

Approx -65mV

Question 6

At what voltage to kv3 open?

Answer 6

Approx -30mv

Question 7

What does the voltage current relationship look like for K+ channels in MNTB neurons with and without Kv3?

Answer 7

Picture an exponential increase curve that look the same up to -30mv
Control will be higher than TEA (blocks kv3)

Question 8

Who did the experiment that showed kv3 channels are in MNTB neurons?

Answer 8

Brew and forsythe 1995

Question 9

Who did the experiment that showed kv1 channels are in mntb neurons?

Answer 9

Johnson et al 2010

Question 10

What type of experiments can be used to study K+ channels?

Answer 10

Electrophysiological
Immunohistochemical
Pharmacological

Question 11

What are the 3 sections of the node?

Answer 11

Node
Paranode
Juxtaparanode

Question 12

What channels can be found in the node?

Answer 12

VGNa

Question 13

What can be found in the paranode?

Answer 13

CASPR - associated with contactin in myelination

Question 14

What channels can be found in the juxtaparanode?

Answer 14

Kv1.1, kv1.2, kv(beta)2 subunit

Question 15

Kv channels can be found under the myelin sheath. Why is this clinically important?

Answer 15

Conditions such as MS demyelination may expose potassium channels

Question 16

Why are kv1 channels so important?

Answer 16

They maintain a 1:1 relationship between an input and output in the MNTB
since information is the pattern of APs kv1 channels allow maintainance of pattern across the synapse
Chaotic firing in MNTB is observed in kv1 pharmacologically inhibited

Question 17

What do kv3 channel allow for?

Answer 17

Short and fast action potentials

Question 18

How many kv3 genes exist?

Answer 18

4
Kv3.1, 3.2, 3.3, 3.4
Splice variants exist

Question 19

What differences do kv3 N terminal splice variants have?

Answer 19

Different inactivation properties

Question 20

What differences do kv3 c terminal splice variants have?

Answer 20

Different modulators effects of phosphorylation (different tissue expression and regulatory control)
Different variants have different propensities to be phosphorylated

Question 21

What phosphorylates kv3.1 and where does this occur?

Answer 21

PKC

S503

Question 22

What does phosphorylation at serine 503 do to kv3.1 channels?

Answer 22

Reduces k+ current

Question 23

When is kv3.1 dephosphorylated?

Answer 23

After high frequency stimulus which increases kv3.1 current

Question 24

What phosphorylates kv3.2?

Answer 24

PKA

Question 25

What does PKA phosphorylation of kv3.4 cause?

Answer 25

Reduced n terminal inactivation

Question 26

What occurs to action potentials following a preconditioned HFS?

Answer 26

Preconditioning at 600Hz for 20 seconds causes more action potentials to be fired on subsequent stimulation This is not seen on low frequency preconditioning

Question 27

Why does preconditioning at high frequencies cause more action potentials to fire?

Answer 27

Moderate to high sounds activity causes dephosphorylation of kv3.1 channels via calcineurin which increases kv3.1 current

Question 28

What is the benefit of kv3.1 activity being activity dependant?

Answer 28

Allows sustained AP firing at high frequencies meaning more information can be traspnsmitted

Question 29

Kv3.1 is basally phosphorylated in the auditory brain stem true or false?

Answer 29

True | This is attenuated by blocking PKC

Question 30

What does sound activity do to kv3.1b in the ipsilateral cochlear nucleus and contralateral MNTB?

Answer 30

Decreases phosphorylation levels via calcineurin