L6 ion Channels

Explain the structure and function of ion channels

Discuss characteristics and examples of ligand-gated ion channels

Discuss characteristics and examples of voltage-gated ion channels

  1. What are Ion Channels?

    • Selective, Integral Proteins

      • Na+, K+, Ca++, Cl-

  2. Do Ion Channels require energy?

    • No

  3. What is the speed like for ion channel signaling?

    • Fast signaling

  4. What are the 3 states of ion channels?

    1. Open

    2. Closed

    3. Inactivated

  5. What are the 2 characteristics of ion channels

    1. Mean Open Time

    2. Probability of Opening

  6. Who won the Novel Prize in Physiology or Medicine 1991 for their discoveries concerning the functions of single ion channels in cells

    • Erwin Neher and Bert Sakmann

  7. What targets ion channels?

    • Drugs

  8. What are the 2 examples given for Blocking Ion Channels

    • Sodium (Na+) Channel Blockers

      • Anti-arrhythmic drugs

      • Local Anesthetics

    • Calcium (Ca+) Channel Blockers

      • Anti-arrhythmic

      • Antianginal drugs

  9. What was the example given for ion channel activation

    • GABAA agonists → Antianxiety

  10. What are Channelopathies

    • Diseases that affect Ion Channels in Excitable and Nonexciteable cells

  11. How are Channelopathies produced

    • Mutation in Single Ion Channels

  12. What are Channelopathies in Excitable Cells?

    • Periodic Paralysis

      • K+/Ca++/Na+ Channels

    • Myasthenia

      • Nicotinic Acetylcholine Receptor

    • Myotonia

      • K+

    • Malignant Hyperthermia

      • Ca++ channel

      • Ryanodine Receptor

    • Long QT Syndrome

      • Na+ & K+ Channels

  13. What are Channelopathies in Nonexcitable Cells

    • Cystic Fibrosis

      • Cl- Channels

    • Bartter Syndrome

      • K+ Channels

  14. What are the 3 Types of Ion Channels?

    1. Ligand-gated

      • binding of the ligand allows the channel to change/open

      • allows influx

    2. Voltage-gated

      • opens in response to a change in membrane potential

    3. Second Messenger-regulated

      • responds to post-translation modification

  1. What makes up the structure of ion channels

    • Polypeptide subunits

    • Aqueous Pore

    • Gate

    • Selectivity Filter

  2. What happens when an ion channel is open?

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

  3. What are the 3 ways ion channels form pores?

    • K+ Channels

      • 4 subunits

    • Acetylcholine (Nicotinic) Receptor

      • 5 subunits

    • Aquaporin

      • 4 subunits

  4. Cells are placed in an environment where the concentration of extracellular sodium (Na+) is greater than the intracellular concentration of Na+ but the extracellular concentration of calcium (Ca2+) is less than the intracellular concentration of Ca2+. Considering the cells have Na+ and Ca2+ channels which of the following will occur?

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

  5. What is a neurotransmitter

    • signaling molecule

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

    1. Binding of a neurotransmitter (ligand) to an orthosteric site

    2. Conformational change

    3. conducting state — opens

  7. How are ligand-gated ion channels’ gates modulated?

    • binding of Endogenous/Exogenous modulators to Allosteric sites

  8. 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

  9. List examples of excitatory, cation-selective ligand-gated ion channels

    • Nicotinic Acetylcholine Receptors (nAchR)

    • Ionotropic Glutamate Receptors

    • 5-HT3 Receptors

    • P2X Receptors

  10. List examples of Inhibitory, anion-selective ligand-gated ion channels

    • GABAA Receptors

    • Glycine Receptors

  11. 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

  12. What are the 4 examples of voltage gated ion channels

    • Na+ channel

    • Ca++ channel

    • K+ channel

    • Cl- channel

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

    • 143

  14. List the subfamilies of Voltage Gated Ion Channels 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) (* not voltage-gated)

    • Transient Receptor Potential channels (TRP) (* not voltage-gated)

    • Voltage-gated proton channel (Hv1)

    • Some of the ion channels placed under the 'Voltage-gated' umbrella are not in fact gated by voltage (eg, KIR, K2P, RyR,TRP)

  15. What is the NMDA receptor for glutamate?

    • Ligand gated Ca++ channel

  16. What voltage gated channel is present in most excitable cells

    • Ca++ channels (Cav)

  17. What type of complexes do Ca++ channels form?

    • Hetero-Oligomeric Complexes

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

    • pore-forming

    • provides binding sites for all agonists and antagonists

  19. 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)

  20. What is the function of K+ Channels?

    • Regulates excitability and controls the shape of the action potential

  21. What type of cells has K+ channels?

    • all cells in the body

  22. What functions do K+ channels involve in?

    • Cognition, Muscle Contraction, Hormone Secretion

  23. How are K+ Channels divided?

    • families based on their structural and functional properties

  24. 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)

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

    • membrane of most excitable cells

  26. What subunits does NaV channels’ one pore-forming Alpha subunit associates with?

    • 1-2 Beta subunits

  27. Explain the composition of NaV Alpha subunits

    • 4 Homologous Domains (I-IV)

  28. What are the contents in each of the 4 Homologous Domains?

    • 6 Transmembrane Segments (S1-S6)

    • Pore-Forming Loop

  29. What is the function in S4?

    • a positively charged voltage sensor that’s involved in channel gating

  30. What is Refractoriness

    • a set period of time where a voltage channel cannot be reactivated