Potassium structure Flashcards
Selectivity filter
TXGYGD MacKinnon 03/05 - P loop
What varies between Kv’s?
NTD and CTD typically short but can vary
Some can be heterotetrameric
Different alpha - each Kv gene encodes a Kva
Similar features of Kv’s?
Ampiphilic helix between S4 + S5 - links to S6T and next subunit
S6T does what
regulates open/close kv gates
PXP - typically valine for X
Non-specific blockers of Kv’s
4-AP + TEA Grissler 1994
A types
Shaker Kv1.4
All Shal Kv4
Shaw Kv3.3 + 3.4 - Birnbaum 2004
Structural differences of A type
Long NTD - ball and chain inactivation
Why is A-type inactivation N-type inactivation
Hoshi 1990
cytoplasmic trypsin - increase open duration and mean number of opening and burst
A-type effects on AP
- activate relative -ve
2. open in response to stimulus before cell reaches threshold
3. recover from inactivation when hyperpolarised (by IDr)
A-type functional properties
- Delay between 1 AP and next (depends on stimulus size + type of A channel
- Regulate firing frequency, spike initiation + waveform -
- Regulate backward spread of AP and integration of EPSP Hoffman 1997
DR includes
Kv1 except 1.4, 2, 3.1, 7, 10.1
Structure of DR
Same as A without NTD inactivation particle
Current of DR
Outwardly rectifying with delay following dep. - prolonged and sustained current due to lack of N-type inactivation
DR functional properties
set neuronal RMP
IM - inhibitory influence on excitabiliy that counters repetitive or burst firing w/o affecting single AP’s
Inward rectifiers
Kir1-7
Structure of Kir6.1/6.1
SUR 4 subunits (SUR1,2A, 2B) 4 Kir6.1/6.2
Kir function
frequency help set rmp
Kir6.1/6.2 function
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
Where are NBD of SUR
Between TMD1 and end of TMD2
Where does ATP and ADP bind on SUR/Kir
Between TMD1 +2 - end of TMD2 (ADP) and between M1 and M2
Ca2+ dep conductances
BK - 100-300pS
SK 1-25 pS
IK 25-100pS
SK families
1-3
Calcium bowl
RCK 2 - string of negative charges - cradle
BK structure
alpha + 4 beta subunits - 1+4 excitatory
BK current
Activated by voltage- become more active as membrane depolarizes or as IC ca2+ levels rise ( outwards rectification)
BK functional properties
- help repolaarize membrane + turn of Ca2+ channels - end ecocytosis
- -ve feedback in response to raised IC ca2+
- smooth muscle relaxation - Brenner 2000 - KO -intention tremor, slow wim speed - decrease stride length
SK structure
Calmodulin in CTD confers ability to respond to Ca2+
SK current
can only be opened by increase IC ca2+ S4 less positive charges
Functional properties of SK
- Hyperpolarization of cells after AP
- Ca2+ influx through synaptic NMDAR - activate SK -> hyperoplarize -> restore Mg2+ blcok
- Participate in vasoregulation , auditory tuning + circadian rhythm
K2P members
15 - 5 categories - TREK, TWIK, TASK, THIK and TALK
K2P structure
- 2 kir sown together
2. pore cap - helical regions of receptor protein
3. 2 subunits form channel
Significance of pore cap
- Prevents block by peptide toxins and small molecules - insensitive to TEA - that typically bind to ecternal mouth and pulg pore
- prevent efflux in vertical domain
- Facilitates partial rehydraation of K+ as they exit - outward rectification
Functional purpose of K2P
RMP
Functional purpose of IKCA
RBS channel activation - reduction inc ell volume - K+ effluc with Cl- and H20
