Ion Channels Lecture Flashcards

A set of 50 flashcards covering the molecular structure, classification, function, and pathology of ion channels based on the lecture by Dr Polly Gravells.

What is the definition of an ion channel in cells?

A transmembrane protein that transports molecules from one side of the membrane to the other.

Which specific ions are mentioned as being transported by ion channels?

$Na^+$, $K^+$, and $Cl^-$ ions.

What are the three main classifications of ion channels based on gating and opening?

Ligand gated channels, Voltage gated channels, and Open/leakage channels.

How do ion channels facilitate high-speed communication in nerve and muscle cells?

By regulating membrane potentials.

What is the purpose of $Ca^{2+}$ influx into the cytoplasm through ion channels?

To trigger processes such as secretion and muscle contraction.

What is the basic structural composition of all ion channel transmembrane proteins?

Two or more $\alpha$-helices that cross the lipid bilayer.

On what properties are subgroups of ion channels classified?

Gating mechanism and ion selectivity of the pore.

The ion selectivity of a pore is defined by which two factors?

The physical size of the 'filter' and the amino acids lining the pore.

How many genes in humans code for membrane channels?

400 genes.

Which bacterium provides the pH-regulated K+ channel KcsA used as a model for all channels?

Streptomyces lividans.

What structural feature forms the highly selective p-loop in a simple $K^+$ channel?

TM helicase structures.

What three factors control the gate located on the cytoplasmic side of an ion channel?

Membrane potential, mechanical stress, and ligands.

What causes the creation of action potentials in excitable cells?

The movement of $Na^+$ and $K^+$ ions.

How do voltage-gated ion channels differ structurally from simple ion channels?

They possess additional helices $S1$ and $S4$ that form a separate 'voltage sensing domain'.

Where in the voltage-gated channel is the voltage sensing domain located?

Lateral to the subunits.

What is the 'plugging mechanism' in a voltage-gated ion channel?

Large polypeptides that extend into the cytoplasm to block the channel.

In a voltage-gated $K^+$ channel, what happens to the $S4$ helix when a potential difference is detected?

The $S4$ helix is pulled away, opening the gate.

How many subunits make up a simple KcsA channel?

4 subunits.

How many helices cross the lipid bilayer in a voltage-gated $Na^+$ or $Ca^{2+}$ channel?

24 helices.

Which type of channel is controlled by either intracellular or extracellular chemical transmitters?

Ligand-gated ion channels.

What is the primary role of extracellular ligand-gated ion channels in neurons?

Cell-to-cell communication via neurotransmitters.

How do $Cl^-$ selective channels affect membrane excitability?

They hyperpolarize cells and reduce action potential firing.

Why is the diversity of subunits in ligand-gated ion channels important for pharmacology?

It provides complexity and opportunities for specific drug targeting.

Which nAChR subunit is specifically cited as being involved in reward pathways and nicotine addiction?

nACh$\alpha 4$.

What is the assembly type of the Cys-loop receptor, such as the nicotinic acetylcholine receptor?

Pentameric assembly (5 subunits).

In a muscle nAChR, which five subunits compose the receptor?

$\alpha, \beta, \gamma, \delta, \text{ and } \epsilon$.

How many transmembrane helices ($TMs$) does each subunit of the nicotinic Ach receptor have?

4 $TMs$ ($M1$, $M2$, $M3$, and $M4$).

Which transmembrane helix lines the pore of the nicotinic Ach receptor?

$M2$.

Which nAChR subunit combination has a high affinity for the agonist varenicline?

$\alpha 4 \beta 2$.

What happens to nAChRs in the cortex and hippocampus following chronic exposure to nicotine?

Receptor upregulation occurs.

Polymorphisms in which two subunit genes are linked to tobacco dependence?

$CHRNA4$ ($\alpha 4$) and $CHRNA6$ ($\alpha 6$).

What medical condition is caused by mutations in the $M2$ region of the human $\alpha 4$ nicotinic subunit?

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).

How does ADNFLE affect neurotransmitter release?

It causes increased nicotinic-mediated transmitter release due to enhanced receptor function.

What is the main neurotransmitter in the brain?

Glutamate.

How are glutamate receptors assembled?

They are tetramers (tetrameric assembly) formed as a dimer of dimers.

Where is the ligand-binding site located on a glutamate receptor?

In a cleft that 'closes' when occupied.

Which glutamate receptor mediates fast excitatory synaptic transmission in the central nervous system?

AMPA receptors.

Which glutamate receptor is slower than other isoforms and involved in learning and memory?

NMDA (N-methyl-D-aspartate) receptor.

The Kainate receptor is associated with which human diseases?

Schizophrenia, depression, and Huntington's disease.

What are the two splicing isoforms of AMPA receptor subunits that affect kinetic properties?

Flip and flop.

How does the 'flop' isoform of the AMPA receptor compare to the 'flip' isoform?

Flop has a faster desensitization rate and reduced current responses to glutamate.

What codon change occurs during RNA editing at the GluA2 Q/R site?

A glutamine ($Q$) codon ($CAG$) is changed to an arginine ($R$) codon ($CGG$).

Where is the GluA2 Q/R site located within the subunit?

In the $M2$ region, inside the channel pore.

What happens to neurons during a stroke due to overstimulation of NMDA receptors?

Neuron death occurs.

What is the pathological consequence of downregulating GluA2 Q/R editing in ALS patients?

An increase in $Ca^{2+}$ permeable AMPA receptors causes damage due to glutamate excitotoxicity.

Which enzyme is responsible for the editing of the GluA2 Q/R site?

ADAR2.

How many ATP molecules are required to open a P2X receptor channel?

3 ATP molecules.

How many transmembrane helices are found in each of the 3 subunits of a P2X receptor?

2 TM helices.

What does the sodium-potassium pump do to maintain the electrochemical gradient?

It pumps 3 $Na^+$ out for every 2 $K^+$ in using ATP.

During the resting stage of a cell, is the membrane more permeable to $Na^+$ or $K^+$?

The cell is more permeable to $K^+$.