This document discusses potassium (K+) channels. It begins with an introduction and overview of K+ channel architecture and classification. It then covers the selectivity filter that allows for selective potassium ion permeation. The document discusses the structural basis of ion permeation and selectivity, including the knock-on ion conduction mechanism and dehydration barrier. It also addresses two conduction states that K+ channels can operate in and how they are selectively permeable while also operating quickly. The document concludes with sections on genetic K+ channelopathies and drugs that can open or block K+ channels.

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