L6 ion Channels

What are Ion Channels?

Selective, Integral Proteins that include Na+, K+, Ca++, Cl-.

Do Ion Channels require energy?

No.

What is the speed like for ion channel signaling?

Fast signaling.

What are the 3 states of ion channels?

Open, Closed, Inactivated.

What are the 2 characteristics of ion channels?

Mean Open Time, Probability of Opening.

Who won the Nobel Prize in Physiology or Medicine 1991 for their discoveries concerning the functions of single ion channels in cells?

Erwin Neher and Bert Sakmann.

What targets ion channels?

Drugs.

What are the 2 examples given for Blocking Ion Channels?

Sodium Channel Blockers (Anti-arrhythmic drugs, Local Anesthetics), Calcium Channel Blockers (Anti-arrhythmic, Antianginal drugs).

What was the example given for ion channel activation?

GABAA agonists → Antianxiety.

What are Channelopathies?

Diseases that affect Ion Channels in Excitable and Non-excitable cells.

How are Channelopathies produced?

Mutation in Single Ion Channels.

What are Channelopathies in Excitable Cells?

Periodic Paralysis, Myasthenia, Myotonia, Malignant Hyperthermia, Long QT Syndrome.

What are Channelopathies in Non-excitable Cells?

Cystic Fibrosis, Bartter Syndrome.

What are the 3 Types of Ion Channels?

Ligand-gated, Voltage-gated, Second Messenger-regulated.

What makes up the structure of ion channels?

Polypeptide subunits, Aqueous Pore, Gate, Selectivity Filter.

What happens when an ion channel is open?

Very rapid diffusion of ions go down the concentration gradient (~ 108 ions/s).

What are the 3 ways ion channels form pores?

K+ Channels (4 subunits), Acetylcholine (Nicotinic) Receptor (5 subunits), Aquaporin (4 subunits).

What occurs when Na+ and Ca2+ channels are present with differing extracellular concentrations?

Na+ being transported along its gradient through a Na+ channel.

What is a neurotransmitter?

Signaling molecule.

Explain the steps of an activated Ligand-Gated Ion Channel.

Binding of a neurotransmitter (ligand) to an orthosteric site, conformational change, conducting state — opens.

How are ligand-gated ion channels’ gates modulated?

Binding of Endogenous/Exogenous modulators to Allosteric sites.

What is the function of Ligand-Gated Ion Channels (LGIC)?

Fast synaptic transmission in CNS and Neuromuscular Junction; has excitatory, inhibitory, and post-synaptic potential.

List examples of excitatory ligand-gated ion channels.

Nicotinic Acetylcholine Receptors (nAchR), Ionotropic Glutamate Receptors, 5-HT3 Receptors, P2X Receptors.

List examples of inhibitory ligand-gated ion channels.

GABAA Receptors, Glycine Receptors.

List examples of non-excitatory/inhibitory ligand-gated ion channels.

Epithelial Sodium Channel (ENaC), Acid-Sensing (Proton-Gated) Ion Channels (ASICs), Zinc-Activated Channel (ZAC), IP3 Receptors.

What are the 4 examples of voltage gated ion channels?

Na+ channel, Ca++ channel, K+ channel, Cl- channel.

How many genes in the human genome are encoded in Voltage-Gated Ion Channels (VGIC)?

List the subfamilies of VGIC.

Voltage-gated calcium channels (CaV), Voltage-gated sodium channels (NaV), Potassium channels, CatSper and Two-Pore channels (TPC), Cyclic nucleotide-regulated channels (CNG), Ryanodine receptors (RyR), Transient Receptor Potential channels (TRP), Voltage-gated proton channel (Hv1).

What voltage gated channel is present in most excitable cells?

Ca++ channels (Cav).

What type of complexes do Ca++ channels form?

Hetero-Oligomeric Complexes.

What is the purpose of Alpha1 Subunits in Ca++ channels?

Pore-forming; provides binding sites for all agonists and antagonists.

What are the 3 families of Alpha1 subunits?

High-Voltage Activated Dihydropyridine-Sensitive Channels (L-Type, CaV1.x), High-Moderate-Voltage Activated Dihydropyridine-Insensitive Channels (CaV2.x), Low-Voltage-Activated Channels (T-Type, CaV3.x).

What is the function of K+ Channels?

Regulates excitability and controls the shape of the action potential.

What type of cells has K+ channels?

All cells in the body.

What functions do K+ channels involve in?

Cognition, Muscle Contraction, Hormone Secretion.

How are K+ Channels divided?

Families based on their structural and functional properties.

List the K+ channel families.

Voltage-gated potassium channels (KV), Calcium & Sodium Activated Potassium Channels (KCa, KNa), Inwardly Rectifying Potassium Channels (KIR), Two Pore Domain Potassium Channels (K2P).

Where are Voltage-Gated Na+ Channels (NaV) located?

Membrane of most excitable cells.

What subunits does NaV channels’ one pore-forming Alpha subunit associate with?

1-2 Beta subunits.

Explain the composition of NaV Alpha subunits.

4 Homologous Domains (I-IV), each with 6 Transmembrane Segments (S1-S6) and a Pore-Forming Loop.

What is the function of S4?

A positively charged voltage sensor that’s involved in channel gating.

What is Refractoriness?

A set period of time where a voltage channel cannot be reactivated.