Ligand and Voltage Gated Ion Channels

1
Lecture 15

• Ligand and Voltage Gated Ion Channels

2
Ion Channels

• Hydrophilic pores
• Ion selective(Na vs K)
• Gated
• Ligands
• Voltage
• Not saturable
• Diffusion limited

Vt
Sout
3
Selectivity of Ion Channels
4
Measuring Ion Channel Activity

• Not catalytic no product
• Convert ionin to ionout
• Carry electrical current

5
Patch-Clamp Method (Neher Sakmann)
6
Neurotransmission

• Ligand gated channels
• Voltage gated channels

7
Classes of ligand gated ion channels

• Extracellular ligands (Acetylcholine family)
• Anion or cation channels
• Oligomeric channels -each subunit with 4 membrane
  spanning helixes
• Intracellular ligands
• Respond to cGMP,cAMP,ATP
• Multiple subunit-each with 6 membrane spanning
  helices

8
Extracellularly Activated, Transmitter-Gated Ion
Channels
9
Signals
10
Acetylcholine Receptor
Neher, E., B. Sakmann Scientific American March
1992, 44-51.
11
Overall Structure
Changeux, J. Scientific American November 1993.
12
Neurotransmitter Binding Site
Changeux, J. Scientific American November 1993.
13
Ion Channel Conformational Change
14
A Different Acetylcholine Receptor
Lodish, Berk, Zipursky, Matsudaira, Baltimore,
Darnell. Molecular Cell Biology 4e. 2000, 949.
15
Ion Channels
Lodish, Berk, Zipursky, Matsudaira, Baltimore,
Darnell. Molecular Cell Biology 4e. 2000, 934.
16
Intracellularly Activated, Transmitter-Gated Ion
Channels
Ope
rat
or
l
i
ga
nd
I
on se
l
ec
tiv
i
ty


c
G
M
P
(p
h
oto
r
ecep
t
o
r
s)
N
a
, K


c
AMP,
cG
MP
(o
l
f
a
ct
o
r
y
ne
u
ro
n
s)
N
a
, K

ATP
(ch
a
nne
l
-c
l
osi
ng
)
K
I
ns(
1,4,5
)
P

(or
ga
n
e
l
l
es
an
d
3
2

C
a
p
la
s
ma
me
m
b
ra
ne)
17
Voltage gated ion channels
18
Mechanism of Voltage Gating
19
Toxins that act on ion channels