Ion Channels Flashcards
What properties did Hodgkins and Huxley predict that ion channels must have?
1) These channels must be capable of allowing ions to move across the membrane at high rates
2) These channels must make use of electrochemical gradient
3) These channels must be able to selectively differentiate between Na+ and K+
4) Must sense voltage (membrane potential) somehow
What properties did Hodgkin and Huxley not anticipate about the channels?
The mechanisms of Na+ inactivation
What is patch clamping?
Allows the measurement of individual ion channels through “patches of the membrane”. A tretched out thin pipette places a suction seal on the membrane surface .
What are the 4 configurations of patch clamping?
1) Cell attached recoding
2) Whole-cell recording
3) Inside out recording
4) outside out recording
What are microscopic currents?
The currents flowing through single channels
What are macroscopic currents?
Currents flowing through a large number of channels.
What is the evidence that single channel can let many ions pass through the membrane at a high rate
A microscopic current is small but large enough (1 pA) to reflect the flow of thousands of ions per millisecond
Evidence that channels are selective?
The use of tetrodotoxin shows that it blocks the microscopic Na+ current like in the macroscopic current.
What makes the frog oocyte a useful expression system for studying ion channel proteins?
They are gigantic and perfect for injecting rna proteins.
Since they are a oocyte, the altered gene can ensure that the membrane protein (channel) is the one injected.
What is response of individual Na+ channels when depolarized?
Individual channels open and close in a random manner. Most of the channels open at the beginning of a prolonged depolarization but the probability of them opening later is less because of inactivation. When all the microscopic currents are averaged they are similar to the macroscopic Na+ response.
What is the response of individual K+ channels when depolarized?
Individual K+ channels fail to inactivate during brief depolarizations.
What is meant by the statement that ion channels and active transporters have complementary functions?
Active transporters create and maintain the ion concentration gradients needed for the ion channels.
Active transporters will accumulate ions by transporting them against their gradient.
What must all active transporters be able to do?
All active transporters must be able to transport ions against their concentration gradient.
How did X-Ray crystallography contribute to knowledge on ion channels?
Using bacteria K+ channels, the channel protein was condensed into a crystal for X-ray diffraction. This experiment revealed the subunit and pore structure of the K+ channel.
What do all the voltage gated ion channels have in common?
They all have transmembrane domains that form pores, a selectivity filter and structures for sensing membrane potential and for gating pore opening and closing.
What structural feature of K+ accounts for its selectivity?
The selectivity filter:
K+ channels are two subunits that each cross the membrane twice with a pore loop. The pore loops forma channel pore that is perfectly made for K+. The narrowest part is too small for bigger ions and too big for small ions because the the pore walls are too far to dehydrate them.
What structural features of K+ channels account for voltage sensitivity?
Each channel subunit has 4 additional transmembrane structures. They have positive charges that enable movement in response to changes in membrane potential.
1) Depolarization pushes the sensors outward
2) Hyperpolarization pulls them inward
Pulling the channel pore open or pushing it closed.
What structural features of K+ channels account for ion conductance?
When there are multiple K+ ions in the selectivity ilter, there is electrostatic repulsion to help speed their transit through the filter.
What is the structure of Na+ channels?
6 membrane spanning regions repeated 4 times -> 24 transmembrane regions. The SF is narrower than that of the K+ channel. Have beta subunits to regulate function.
Why are K+ channels so diverse?
Helps to diversify functions and properties of neurons.
What do Cl- channels help with?
They contribute to excitability, resting potential and help regulate cell volume.
What is the structure of Cl- channels?
Has dimers of two identical subunits. Each subunit has an ion-coducting pore (each complete Cl- channel as 2 pores).
Do not have a voltage sensor attached!
If Cl- channels do not have voltage sensors like the other channels, then how do they sense voltage?
Voltage dependent movement of a negatively charged amino acid near the selectivity filter.
What are the 4 types of ion channels?
1) Voltage dependent
2) Ligand gated
2) Thermosensitive channels
4) Mechanosensitive channels
What are the most important ligand-gated ion channels in the nervous system?
Neurotansmitter receptors
Differences between voltage gated and ligand gated channels?
How they are activated: change in membrane potential vs the binding of a chemical signal
Generally most voltage gated channels are selectively permeable but the ligand gated ones are less selective.
What does ASIC stand for?
Acid-sensing ion channels ( Na+ channels that respond to H+ and not voltage)
What are the two types of active transporters?
ATPase pumps and ion exchangers
What are the sources of energy for the two types of active transporters?
ATPase pumps get energy from hydrolysis of ATP.
Ion exchangers use the electrochemical gradients of other ions as a chemical source
What is an example of ATPase pump?
Na+/K+ pump, Ca2+ pump
How does the Na+/K+ pump function?
For every 2K+ pumped out of the cell, 3 Na+ gets pumped into the cell. Phsophorylation will change the shape of the pump to accomodate the pumping.
what are the two types of ion exchangers?
Antiporters and Co-transporters
What is an example of an antiporter?
Na+.Ca2 exchanger
How do we distinguish the two types of Ion exchangers?
Based on the direction of ion movement
Antiportes exchnage intracellular and extracellular iosn but co-transporters carries multiple ions in the same direction.
What are some examples of co-transporters?
Na+/K+/Cl- co-transporter and the K+/Cl- co-transporter
Although the Na+/K+ pump is electrogenic, it makes only a minor contribution to the neuron’s resting potential. Explain why.
Na+/K+ pumps works very slowly because it is an active process that requires steps and sequences to pump ions.
