different types of potassium channels..their structure and functions..

2. 
Introduction

K+ channel architecture

Selectivity filter

Ion permeation

K+ channelopathies

Drugs

3. 
Ion channels are integral proteins

Plays a vital role in functioning of a cell

Genetic identification of ion channels has
improved our understanding……….

Ion channels
enzymes…

4. Intracellular
volume is ~10–12
Ion permeate
at the rate of
107/s
Intracellular k+
concentration
100 mM
After one sec
there will be
no k+ in cell

5. Hence to b effective in altering the
membrane potential …………….
 The opening & closing of channel should be
brief and fast……….
Structural basis of
permeation & selectivity

6. 

-KcsA
4 sub units are clustered to form to
form ion permeation pathway..

About 78 human genes have been
identified yet…..

K+ channels are tetramers composed of
four alpha subunits..

7. CLASSIFICATION OF K+ CHANNELS
6TM/P
22TM/P
8TM/2P
4TM/2P

8.  2TM/P is essentially a universal feature of k+
channel
 it has amino tetramerization domain, carboxy
terminal, protein interacting domain..
 standard nomenclature of these channels was
proposed by Nomenclature and Drug
Classification International Union of Basic and
Clinical Pharmacology Committee on Receptor
Nomenclature and Drug classification (NCIUPHAR)

9. 2 TM Family

10. 4 TM Family

11. 6 TM Family

12.  How are k+ channels selective…..?
Selectivity filter
T
V
G
Y
G
~12 Å
~2.5 Å
Series of
stereo
chemical
check points

13. Ion permeation
 k+ channel should operate under two
constraints…..
strictly selective & quick
 Strategies
Knock-on ion
conduction
Dehydration
barrier
Two
conduction
states

14. Knock-on ion conduction
The dehydration barrier

15. Two conduction modes
 Higher conduction state 500 ps
k+ more than 20mM
 Lower conduction state
less than 20mM

16. K+ Channelopathies
 Cardiac diseases (KvLQT1)
CNS diseases (KCNA1)
Deafness (KCNQ4)
Renal diseases(KCNJ1)
Metabolic diseases (SUR1)

17. DRUGS
K+ Channel openers

19. K+ channel blockers