Part 2 Ion Channels and Pumps in Neuroscience

A comprehensive set of flashcards based on key concepts from the lecture on ion channels and pumps in neuroscience.

How do channel kinetics differ between sodium and potassium channels?

Sodium channels open quickly and close quickly, while potassium channels are slower to open and slower to close.

What happens to Na+ channels and K⁺ channels during depolarization?

Na+ channels inactivate during depolarization but K⁺ channels do not inactivate during depolarization. (both channels open in response to depolarization, but sodium channels then inactivate) ​

How does hyperpolarization affect Na+ and K+ channels?

Hyperpolarization closes both Na+ and K+ channels.

What is the probability of opening Na+ and K+ channels influenced by?

The probability of opening is increased by depolarization.

What structural feature do voltage-gated K+ channels have?

They are composed of 4 subunits, each corresponding to a repeated domain of voltage-gated Na+ channels, with 6 TM segments.

What is the role of inward-rectifying channels?

They help regulate and maintain the resting membrane potential by being open at rest and closed during depolarization. They are composed of 4 subunits.

What distinguishes glutamate receptor channels from other channels?

They have an extracellular amino terminus and a P region that enters and exits the cytoplasmic side of the membrane.

How many K+ channel genes are known?

Nearly 100 K+ channel genes are known. K+ channels are the most numerous and most diverse​

What is an example of gating differences in K+ channels?

Some K+ channels show little inactivation, while others inactivate during depolarization.

What do voltage-gated Na+ and K+ channels have in common?

Both are comprised of 4 subunits (domain) and each subunit has 6 transmembrane segments (S1-S6).

What forms the pore of a voltage-gated channel?

The P-region forms the pore of the channel, part of the selectivity pore.

Note that the domains (motifs) of sodium channels are connected to?

form a single polypeptide chain.

What did patch clamp studies confirm about Na+ and K+ channels?

They confirmed that voltage-gated Na+ and K+ channels are responsible for the macroscopic conductances and currents underlying action potentials.

What effect do α-toxins have on Na+ channels?

They slow the inactivation of Na+ channels, prolonging the action potential.

What is the result of the action of α-toxins on Na+ channels?

the scrambling of information flow (signals) within the nervous system ​

What is the result of the action of β-toxins on Na+ channels?

They shift the voltage dependence of Na+ activation, this downshift in voltage dependence causes the channel to open at more negative potentials​ and the end result is uncontrolled action potential firing.

How was the structure of the bacterial K+ channel revealed?

It was revealed through X-ray crystallography.

Describe the structural features of the bacterial K+ channel, particularly its pore and selectivity filter.

The channel is formed by 4 subunits that each cross the membrane twice.

• The pore loop, between the two helical structures of each subunit, is inserted into the membrane.

• The channel pore is formed by the pore loops of each subunit as well as by the membrane-spanning domains.

• The selectivity filter allows non-hydrated K+K+ ions to fit through.

What is the main difference between larger cations and Na+ regarding the bacterial K+ channel?

Larger cations cannot traverse the channel, and smaller cations like Na+ cannot enter because the pore walls are too far apart to stabilize a dehydrated Na+​.

What additional structure does the mammalian voltage-gated K+ channel have?

It has a β-subunit and a T1 domain. it also revealed similar characteristics like those found in the bacterial K+ channel.

Likewise, each channel subunit has 4 additional transmembrane structures that form the voltage sensors of the channel​

What do the positive charges in voltage sensors of mammalian K+ channels do?

They enable movement within the membrane in response to changes in membrane voltage.

How is the movement of voltage sensors transferred to the channel pore?

The voltage sensors are connected to the channel pore by helical linkers, which transfer any movement by the voltage sensors to the channel pore.

What happens to voltage sensors during depolarization?

Depolarization pushes the voltage sensors outward, opening the pore.

What happens to the voltage sensors during hyperpolarization?

Hyperpolarization pulls the voltage sensors inward, closing the pore.

How do channels differ from pumps in terms of gating?

Channels, once opened, provide for a continuous aqueous pathway across the cell membrane - a pathway controlled by “gating”​, that control ion flux.

What distinguishes pumps from channels?

Pumps typically have two gates. These two gates are never opened at the same time, but both can close at the same time. Binding of an ion (or ions) results in conformational changes with the protein pump in a sequential order of events.

What is characteristic of active transporters compared to ion channels?

Ion flux via active transporters is much slower than ion flux through channels.

Active transporters generate and maintain concentration gradients and translocate ions against their electrochemical gradients.

What distinguishes pumps from channels?

Pumps typically have two gates and engage in sequential conformational changes upon ion binding.

What are the two main classes of neuronal transporters and how do they function?

Neuronal transporters are divided into two main classes:

1. ATPase pumps: (e.g.,the Na+-K+ pump and the Ca+2 pump) 

2. Transporters: This class includes:

   • Ion exchangers: (e.g., the Na+/Ca+2 exchanger and the Na+/H+ exchanger) use the movement of Na+ to drive the movement of Ca+2 and H+

   • Cotransporters: These carry multiple ions simultaneously in the same direction across the membrane.

Although the electrochemical gradient of Na+ is the primary /initial source of energy for both ion exchangers and cotransporters, these gradients ultimately depend on the hydrolysis of ATP by ATPase pumps​

What is the role of ATPase pumps?

They maintain concentration gradients for ions like Na+ and K+.

What is an example of an ATPase pump?

The Na+-K+ pump (Na+-K+ ATPase pump).

What The Na+-K+ pump (aka the Na+ pump, the Na+-K+ ATPase pump) is responsible for?

maintaining the concentration gradients for both Na+ and K+​

What is the effect of an extracellular domain on the Na-Kpump that binds ouabain?

It blocks the pump, leading to loss of ion gradients and resting membrane potential.

What does the Ca+2 pump do in mammalian cells?

It removes intracellular Ca+2 ions.

What are the two types of pumps mentioned?

The PMCA for plasma membranes and the SERCA for Ca+2 storage in the endoplasmic reticulum.

What did studies using radioactive Na+ show about Na+ efflux?

Na+ efflux is dependent on intracellular ATP and external K+ supply.

What happens to Na+ efflux when ATP supply is interrupted or external K+ is removed​?

Efflux of Na+ ceases.

The opposing fluxes of Na+ and K+ are functionally inseparable ​

How many Na+ are pumped out for every 2 K+ pumped in by the Na+-K+ pump?

3 Na+ are pumped out for every 2 K+ pumped in.

What results from the difference in stoichiometry of the Na+-K+ pump?

A net loss of positive charge from the inside, making it electrogenic.

What do ion exchangers do? (“active” transporters​)

They exchange extracellular and intracellular ions, moving one or more ions uphill while moving another ion, usually Na+, downhill.

What is the purpose of the Na+/Ca+2 exchanger?

To keep the level of intracellular Ca+2 low.

What does the Na+/H+ exchanger regulate?

It regulates intracellular pH.

How does the Ca+2 pump translocate calcium ions?

It uses ATP hydrolysis to move Ca+2 from the cytoplasm into the sarcoplasmic reticulum.

What is similar between the Ca+2 pump and the Na+-K+ pump in terms of function?

Both utilize phosphorylation to induce conformational changes.

How does the ion flux of the Ca+2 pump differ from that of channels?

Unlike ion channels, where flux of an ion occurs through an aqueous pore, in the Ca+2 pump, Ca+2 is sequestered deep inside the protein, away from the aqueous medium.

What typically happens when one of the two gates of a pump opens?

It causes conformational changes in the protein pump.

How does the Na+/Ca+2 exchanger help maintain calcium levels?

By moving Na+ ions downhill to drive the movement of Ca+2 ions uphill.

Why is the action of active transporters considered uphill?

Because they move ions against their electrochemical gradients.

What defines the gating of ion channels?

Gating refers to the mechanism that controls the state of the channel, whether open or closed.

In what manner do mammalian voltage-gated K+ channels respond to voltage changes?

They open or close in response to changes in membrane voltage.

What key feature distinguishes Na+ channels from K+ channels structurally?

Na+ channels have a molecular mechanism for inactivation, while K+ channels generally do not.

What is the significance of the selectivity filter in ion channels?

It allows specific ions like K+ to pass while blocking others such as Na+.

What are the typical consequences of altered gating in Na+ channels due to toxins?

They can result in prolonged action potentials and altered signal transmission.