Channels

1
Channels

• Highly selective
• Two states
• Tightly regulated
• Voltage-gated channels
• Ligand-gated channels
• Spontaneously closing

2
Channel Selectivity
3
Voltage-gated Channels

• Channels open when the membrane potential is
  depolarized.
• Resting state, the membrane potential is -60 mV
• A nerve impulse, the membrane potential will be
  30 mV
• The transient is mediated by the voltage-gated
  channels

4
Voltage-gated Channels

• Channels open when the membrane potential is
  depolarized.

5
Voltage-gated Sodium Channel

• Starts to open when the membrane potential is
  gt-60 mV
• Open quickly
• Inactivates also quickly

6
Voltage-gated Potassium Channel

• Starts to open when the membrane potential is
  gt-40 mV
• Open slowly

7
Voltage-gated Sodium Channel
About 260 kd with four units. Each unit has six
transmembrane helices.
S4 contains positively charged residues, and is
considered as the voltage sensors of the
channels. S5 and S6 form the pore of the channels.
8
Sodium Channel Poison
Isolated from puffer fish
Tetrodotoxin binds to Na channels with Ki 1 nM
9
Voltage-gated Potassium Channel
Determine the selectivity
70 kd with six helices Four subunits come
together to form a functional channel.
10
Voltage-gated Potassium Channel
11
Voltage-gated Potassium Channel
Outside cell
Inside cell
12
Voltage-gated Potassium Channel
TVGYG is a highly conserved in K-channels
13
Selectivity of Potassium Channel
A Larger ones can not pass. B Small
ones can not form the perfect
interactions within the channel.
14
Selectivity of Potassium Channel
15
Rapid Ion Transport of Potassium Channel
16
Selectivity of Sodium Channel
Selectivity of sodium channels is determined by
the diameter of the pore.
17
A Model for Voltage Gating of Ion Channels
18
Closing of the Potassium Ion Channels
Mutant lacking residues 6-46 does not inactivate.
A ball-and-chain model.
Lengthening the chain slows inactivation
19
Ligand-gated Channels

• Acetylcholine receptor channel

Each vesicle contains 104 acetylcholine
20
Ligand-gated Channels

• Acetylcholine receptor channel is equally
  permeable to Na and K

21
Acetylcholine Receptor Channel
Five subunits 2a, b, g and d Acetylcholine
binds at a-g and a-d interfaces The channel
will open for about 1 ms
22
Opening of Acetylcholine Channels
23
Acetylcholinesterase
24
Acetylcholine Receptor Poisons

• Venoms a-bungarotosin and cobratoxin (small
  polypeptides)
• Bind to the receptor tightly
• Some nerve gases
• Block acetylcholinesterase by reacting with
  -CH2-OH of serine residue in the enzyme