Potassium structure

Question 1

Selectivity filter

Answer 1

TXGYGD MacKinnon 03/05 - P loop

Question 2

What varies between Kv’s?

Answer 2

NTD and CTD typically short but can vary

Some can be heterotetrameric

Different alpha - each Kv gene encodes a Kva

Question 3

Similar features of Kv’s?

Answer 3

Ampiphilic helix between S4 + S5 - links to S6T and next subunit

Question 4

S6T does what

Answer 4

regulates open/close kv gates

PXP - typically valine for X

Question 5

Non-specific blockers of Kv’s

Answer 5

4-AP + TEA Grissler 1994

Question 6

A types

Answer 6

Shaker Kv1.4

All Shal Kv4

Shaw Kv3.3 + 3.4 - Birnbaum 2004

Question 7

Structural differences of A type

Answer 7

Long NTD - ball and chain inactivation

Question 8

Why is A-type inactivation N-type inactivation

Answer 8

Hoshi 1990

cytoplasmic trypsin - increase open duration and mean number of opening and burst

Question 9

A-type effects on AP

Answer 9

• activate relative -ve
  2. open in response to stimulus before cell reaches threshold
  3. recover from inactivation when hyperpolarised (by IDr)

Question 10

A-type functional properties

Answer 10

1. Delay between 1 AP and next (depends on stimulus size + type of A channel
2. Regulate firing frequency, spike initiation + waveform -
3. Regulate backward spread of AP and integration of EPSP Hoffman 1997

Question 11

DR includes

Answer 11

Kv1 except 1.4, 2, 3.1, 7, 10.1

Question 12

Structure of DR

Answer 12

Same as A without NTD inactivation particle

Question 13

Current of DR

Answer 13

Outwardly rectifying with delay following dep. - prolonged and sustained current due to lack of N-type inactivation

Question 14

DR functional properties

Answer 14

set neuronal RMP

IM - inhibitory influence on excitabiliy that counters repetitive or burst firing w/o affecting single AP’s

Question 15

Inward rectifiers

Answer 15

Kir1-7

Question 16

Structure of Kir6.1/6.1

Answer 16

SUR 4 subunits (SUR1,2A, 2B) 4 Kir6.1/6.2

Question 17

Kir function

Answer 17

frequency help set rmp

Question 18

Kir6.1/6.2 function

Answer 18

While ATP and ADP bind to IC side causes channel closure - when Mg2+ bound - molecules interact with nucleotide binding domains of SUR to increase channel activity

Question 19

Where are NBD of SUR

Answer 19

Between TMD1 and end of TMD2

Question 20

Where does ATP and ADP bind on SUR/Kir

Answer 20

Between TMD1 +2 - end of TMD2 (ADP) and between M1 and M2

Question 21

Ca2+ dep conductances

Answer 21

BK - 100-300pS

SK 1-25 pS

IK 25-100pS

Question 22

SK families

Answer 22

1-3

Question 23

Calcium bowl

Answer 23

RCK 2 - string of negative charges - cradle

Question 24

BK structure

Answer 24

alpha + 4 beta subunits - 1+4 excitatory

Question 25

BK current

Answer 25

Activated by voltage- become more active as membrane depolarizes or as IC ca2+ levels rise ( outwards rectification)

Question 26

BK functional properties

Answer 26

1. help repolaarize membrane + turn of Ca2+ channels - end ecocytosis 2. -ve feedback in response to raised IC ca2+ 3. smooth muscle relaxation - Brenner 2000 - KO -intention tremor, slow wim speed - decrease stride length

Question 27

SK structure

Answer 27

Calmodulin in CTD confers ability to respond to Ca2+

Question 28

SK current

Answer 28

can only be opened by increase IC ca2+ S4 less positive charges

Question 29

Functional properties of SK

Answer 29

1. Hyperpolarization of cells after AP 2. Ca2+ influx through synaptic NMDAR - activate SK -> hyperoplarize -> restore Mg2+ blcok 3. Participate in vasoregulation , auditory tuning + circadian rhythm

Question 30

K2P members

Answer 30

15 - 5 categories - TREK, TWIK, TASK, THIK and TALK

Question 31

K2P structure

Answer 31

- 2 kir sown together 2. pore cap - helical regions of receptor protein 3. 2 subunits form channel

Question 32

Significance of pore cap

Answer 32

1. Prevents block by peptide toxins and small molecules - insensitive to TEA - that typically bind to ecternal mouth and pulg pore 2. prevent efflux in vertical domain 3. Facilitates partial rehydraation of K+ as they exit - outward rectification

Question 33

Functional purpose of K2P

Answer 33

RMP

Question 34

Functional purpose of IKCA

Answer 34

RBS channel activation - reduction inc ell volume - K+ effluc with Cl- and H20