Role Of Kv1 And Kv3 In Neuronal Excitability Flashcards
Where can kv2.2 channels be found?
Heart and brain
Kv2.1 = neocortex/ hippocampus
Kv2.2 = medial nucleus of the trapezoid body
What happens on kv1 Blockage by dendrotoxin?
For a stimulus which would normally produce a single AP, multiple action potentials will fire.
No increase in threshold
What is the function of kv channels in the brainstem?
Involved in sound localisation
What two factors contribute to sound localisation and where do they input to?
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
At what voltage do kv1 channels active?
Approx -65mV
At what voltage to kv3 open?
Approx -30mv
What does the voltage current relationship look like for K+ channels in MNTB neurons with and without Kv3?
Picture an exponential increase curve that look the same up to -30mv
Control will be higher than TEA (blocks kv3)
Who did the experiment that showed kv3 channels are in MNTB neurons?
Brew and forsythe 1995
Who did the experiment that showed kv1 channels are in mntb neurons?
Johnson et al 2010
What type of experiments can be used to study K+ channels?
Electrophysiological
Immunohistochemical
Pharmacological
What are the 3 sections of the node?
Node
Paranode
Juxtaparanode
What channels can be found in the node?
VGNa
What can be found in the paranode?
CASPR - associated with contactin in myelination
What channels can be found in the juxtaparanode?
Kv1.1, kv1.2, kv(beta)2 subunit
Kv channels can be found under the myelin sheath. Why is this clinically important?
Conditions such as MS demyelination may expose potassium channels
Why are kv1 channels so important?
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
What do kv3 channel allow for?
Short and fast action potentials
How many kv3 genes exist?
4
Kv3.1, 3.2, 3.3, 3.4
Splice variants exist
What differences do kv3 N terminal splice variants have?
Different inactivation properties
What differences do kv3 c terminal splice variants have?
Different modulators effects of phosphorylation (different tissue expression and regulatory control)
Different variants have different propensities to be phosphorylated
What phosphorylates kv3.1 and where does this occur?
PKC
S503
What does phosphorylation at serine 503 do to kv3.1 channels?
Reduces k+ current
When is kv3.1 dephosphorylated?
After high frequency stimulus which increases kv3.1 current
What phosphorylates kv3.2?
PKA
What does PKA phosphorylation of kv3.4 cause?
Reduced n terminal inactivation
What occurs to action potentials following a preconditioned HFS?
Preconditioning at 600Hz for 20 seconds causes more action potentials to be fired on subsequent stimulation
This is not seen on low frequency preconditioning
Why does preconditioning at high frequencies cause more action potentials to fire?
Moderate to high sounds activity causes dephosphorylation of kv3.1 channels via calcineurin which increases kv3.1 current
What is the benefit of kv3.1 activity being activity dependant?
Allows sustained AP firing at high frequencies meaning more information can be traspnsmitted
Kv3.1 is basally phosphorylated in the auditory brain stem true or false?
True
This is attenuated by blocking PKC
What does sound activity do to kv3.1b in the ipsilateral cochlear nucleus and contralateral MNTB?
Decreases phosphorylation levels via calcineurin
