Part 3 molecular and functional characterisation
of voltage-gated potassium channels
Now looking at voltage-gated K channels responsible for the falling phase of an action
potential
There are 2 major types of voltage gated K channels, which was figured out by
electrophysiologists long before molecular biologists got their hands on ion channels
The first channel is ‘’ delayed rectifier’’ K channel
K channel delayed rectifier is involved in AP and are responsible for falling phase of
AP
Respond to depolarisation with a delay
does not activate
Blocked by TEA
Mediate falling phase of AP in squid axon/ most animal with these channels
The second channel is called the ‘’fast’’ and ‘’early’’ channel (KA)-
Respond to depolarisation without delay
inactivate
Blocked by 4-aminopyrimidine (4-AP)
Open rapidly for a short period of time and then closes-Na current
Open for a longer time-K current
2 types of voltage-gated K channel
, This diagram shows schematically the 2 types of current
Molecular characterisation of the voltage-gated K channel was first accomplished by analysis of
Drosophila mutant
Example of a comparative approach
Can easily generate mutants easily
In the mutant Drosophila ‘’shaker’’ the legs shake when the animal is under anaesthesia
(ether)
Electrophysiological analysis of muscle from shaker flies revealed that K A –type currents
were affected by this mutation
Link phenotype to individual current recorded from muscle cells
Cloning and sequencing the shaker gene revealed that it encodes a 616 aa protein (approx.
70kDa) with 6 transmembrane helices, which resembles one domain of a voltage-gated
sodium channel
Voltage-gated Na an K ion channels are related
¼ of voltage gated Na channel is a K channel
Voltage gated Na and K channel are similar in structure, which show that they have a
common shard ancestor
Voltage gated K channels are built from 4 separate proteins
There are 4 genes in drosophila that encode voltage gated K
channels: shaker, shab, shaw, shal
After identifying the shaker gene is was easy for geneticist to
identify other genes
The very first k channel was discovered from the shaker gene
The discovery of the shaker channel led to the discovery of a family related Drosophila gene
encoding voltage-gated K channels with different inactivation properties
of voltage-gated potassium channels
Now looking at voltage-gated K channels responsible for the falling phase of an action
potential
There are 2 major types of voltage gated K channels, which was figured out by
electrophysiologists long before molecular biologists got their hands on ion channels
The first channel is ‘’ delayed rectifier’’ K channel
K channel delayed rectifier is involved in AP and are responsible for falling phase of
AP
Respond to depolarisation with a delay
does not activate
Blocked by TEA
Mediate falling phase of AP in squid axon/ most animal with these channels
The second channel is called the ‘’fast’’ and ‘’early’’ channel (KA)-
Respond to depolarisation without delay
inactivate
Blocked by 4-aminopyrimidine (4-AP)
Open rapidly for a short period of time and then closes-Na current
Open for a longer time-K current
2 types of voltage-gated K channel
, This diagram shows schematically the 2 types of current
Molecular characterisation of the voltage-gated K channel was first accomplished by analysis of
Drosophila mutant
Example of a comparative approach
Can easily generate mutants easily
In the mutant Drosophila ‘’shaker’’ the legs shake when the animal is under anaesthesia
(ether)
Electrophysiological analysis of muscle from shaker flies revealed that K A –type currents
were affected by this mutation
Link phenotype to individual current recorded from muscle cells
Cloning and sequencing the shaker gene revealed that it encodes a 616 aa protein (approx.
70kDa) with 6 transmembrane helices, which resembles one domain of a voltage-gated
sodium channel
Voltage-gated Na an K ion channels are related
¼ of voltage gated Na channel is a K channel
Voltage gated Na and K channel are similar in structure, which show that they have a
common shard ancestor
Voltage gated K channels are built from 4 separate proteins
There are 4 genes in drosophila that encode voltage gated K
channels: shaker, shab, shaw, shal
After identifying the shaker gene is was easy for geneticist to
identify other genes
The very first k channel was discovered from the shaker gene
The discovery of the shaker channel led to the discovery of a family related Drosophila gene
encoding voltage-gated K channels with different inactivation properties
