Chapter 4 – ion channels and transporters
Overview
2 different kinds of proteins in the plasma membrane:
1. Active transporters (pumping station); ion
concentration gradient is established by this. They
actively move ions into or out of cell against
concentration gradient
a. ATPase pumps
i. Na/K pump
ii. Ca pump
b. Ion exchangers
i. Antiporters
1. Na/Ca exchanger
2. Na/H exchanger
ii. Co-transporters
1. Na/K/Cl co-transporter
2. K/Cl co-transporter
3. Na/neurotransmitter co-transporter
2. Ion channels (lock); selective permeability is due to ion channels. They allow
only certain kinds of ions to cross the membrane in the direction of their
concentration gradient.
1. Voltage-gated channels; respond to changes in membrane potential.
The membrane potential alters the conformation of the channel
proteins, resulting their opening and closing. The channels have a
voltage sensor that detect the potential across the membrane.
a. Na channel
b. K channel
c. Ca channel
d. Cl channel
2. Ligand-gated channels; respond to changes chemical signals (ligand).
The chemical signals bind to extracellular or intracellular domains of
these proteins
a. Neurotransmitter receptor
b. Acid sensing ion channel (ASICs)
c. Ca activated K channel
d. Cyclic nucleotide gated channel
3. Thermosensitive channels; respond to heat
4. Mechanosensitive channels; respond to stretch
Transporters create the concentration gradient that help drive ion fluxes through
open ion channels, thereby generating electrical signals
Ion channels underlying action potentials
Patch clamp: technique capable of measuring current flowing
through single channels.
Cell-attached path clamp recording method: measure
the current that flows when a single ion channel opens (membrane stays
intact)
, Whole cell recording; measure the current that flows out of the whole cell
(membrane is damaged)
Microscopic currents: currents flowing through single channels
Macroscopic currents: currents flowing through a large number of
channels
Voltage gated ion channels;
1. Na channel (selectively permeable to Na)
Currents are directed inward (negative)
Ion channels are closed during resting phase, then open at
the beginning of depolarization ((fast) activation gates), then
they become inactivated and pass into a nonconducting state
((slow) inactivation gates) then close during
hyperpolarization
Na channels have additional molecular mechanism
responsible for inactivation
2. K channel (selectively permeable to K);
Currents are directed outward (positive)
Ion channels are closed during resting phase and at the beginning of
depolarization, then they open, then they close during hyperpolarization
Voltage-gated ion channels
Voltage-gated ion channels are selectively permeable to
specific ions (Na, K, Ca or Cl)
Many genes for each type of voltage-gated ion channel.
The different types of channels which are formed by the
different genes vary in their activation and inactivation
properties.
10 Na channel genes (SCN genes)
16 Ca channel genes (CACNA genes)
100 K channel genes (KCN genes) (largest and
most diverse class of voltage-gated ion channels)
Cl channel genes (CLCN genes)
How ion channels work
K+ channels:
Formed by subunits that each cross the plasma membrane twice. Between the
subunits is a pore loop that inserts into the plasma membrane.
In total 4 subunits in K+ channels
From outside to inside
Pore (in the center the 4 pore loops come together to form
this) – water filled cavity – selectivity filter (ion selectivity)
The water filled cavity collects the K+.
The K+ become dehydrated, the naked K+ ions are able to
move through 4 K+ binding sites within the selectivity filter to
reach the extracellular space.
Overview
2 different kinds of proteins in the plasma membrane:
1. Active transporters (pumping station); ion
concentration gradient is established by this. They
actively move ions into or out of cell against
concentration gradient
a. ATPase pumps
i. Na/K pump
ii. Ca pump
b. Ion exchangers
i. Antiporters
1. Na/Ca exchanger
2. Na/H exchanger
ii. Co-transporters
1. Na/K/Cl co-transporter
2. K/Cl co-transporter
3. Na/neurotransmitter co-transporter
2. Ion channels (lock); selective permeability is due to ion channels. They allow
only certain kinds of ions to cross the membrane in the direction of their
concentration gradient.
1. Voltage-gated channels; respond to changes in membrane potential.
The membrane potential alters the conformation of the channel
proteins, resulting their opening and closing. The channels have a
voltage sensor that detect the potential across the membrane.
a. Na channel
b. K channel
c. Ca channel
d. Cl channel
2. Ligand-gated channels; respond to changes chemical signals (ligand).
The chemical signals bind to extracellular or intracellular domains of
these proteins
a. Neurotransmitter receptor
b. Acid sensing ion channel (ASICs)
c. Ca activated K channel
d. Cyclic nucleotide gated channel
3. Thermosensitive channels; respond to heat
4. Mechanosensitive channels; respond to stretch
Transporters create the concentration gradient that help drive ion fluxes through
open ion channels, thereby generating electrical signals
Ion channels underlying action potentials
Patch clamp: technique capable of measuring current flowing
through single channels.
Cell-attached path clamp recording method: measure
the current that flows when a single ion channel opens (membrane stays
intact)
, Whole cell recording; measure the current that flows out of the whole cell
(membrane is damaged)
Microscopic currents: currents flowing through single channels
Macroscopic currents: currents flowing through a large number of
channels
Voltage gated ion channels;
1. Na channel (selectively permeable to Na)
Currents are directed inward (negative)
Ion channels are closed during resting phase, then open at
the beginning of depolarization ((fast) activation gates), then
they become inactivated and pass into a nonconducting state
((slow) inactivation gates) then close during
hyperpolarization
Na channels have additional molecular mechanism
responsible for inactivation
2. K channel (selectively permeable to K);
Currents are directed outward (positive)
Ion channels are closed during resting phase and at the beginning of
depolarization, then they open, then they close during hyperpolarization
Voltage-gated ion channels
Voltage-gated ion channels are selectively permeable to
specific ions (Na, K, Ca or Cl)
Many genes for each type of voltage-gated ion channel.
The different types of channels which are formed by the
different genes vary in their activation and inactivation
properties.
10 Na channel genes (SCN genes)
16 Ca channel genes (CACNA genes)
100 K channel genes (KCN genes) (largest and
most diverse class of voltage-gated ion channels)
Cl channel genes (CLCN genes)
How ion channels work
K+ channels:
Formed by subunits that each cross the plasma membrane twice. Between the
subunits is a pore loop that inserts into the plasma membrane.
In total 4 subunits in K+ channels
From outside to inside
Pore (in the center the 4 pore loops come together to form
this) – water filled cavity – selectivity filter (ion selectivity)
The water filled cavity collects the K+.
The K+ become dehydrated, the naked K+ ions are able to
move through 4 K+ binding sites within the selectivity filter to
reach the extracellular space.
