Lecture 4 - Ligand-gated channels Flashcards

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1
Q

What are cells’ responses to specific stimuli achieved through?

A

Cells respond specifically to particular stimuli using molecules involved in signal transduction.

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2
Q

What are the essential functions of ion channels?

A

Transport ions across the membrane, secretion/absorption of fluids

Regulate membrane potential, nerve and muscle cells

Calcium influx into the cytoplasm, secretion, and muscle contraction

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3
Q

What are the structural features of all ion channels?

A

Transmembrane proteins made up of two or more α-helices that cross the lipid bilayer. They are made up of two to six subunits that usually surround the “pore.” Exceptions are Chloride, water, and ammonia channels that exist in the middle of a single subunit.

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4
Q

What is the structure of a simple ion channel like K+?

A

A simple ion channel like K+ has a TM helicase structure that forms a p-loop (pore) that’s highly selective. On the cytoplasmic side, TMs are more tightly packed, creating a gate.

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5
Q

What are the two main functions of voltage-gated ion channels?

A

Voltage-gated ion channels have two main functions. Na+ and K+ create Aps in excitable cells, while Ca2+ is transported into the cytoplasm where a second messenger elicits a cellular response.

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6
Q

What are the additional helices that form a separate “voltage sensing domain” in VG channels, and what is their function?

A

Voltage-gated ion channels have additional helices S1 and S4 that form a separate “voltage sensing domain” lateral to the subunits. They have large polypeptides that extend into the cytoplasm and act as a plugging mechanism.

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7
Q

What are Transient Receptor Potential (TRP) channels, and how do they differ from VG channels?

A

Transient Receptor Potential (TRP) channels share some structures with VG channels but are evolved to sense chemicals and physical stimuli.

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8
Q

What is the structure of ligand-gated ion channels, and how are they controlled?

A

Ligand-gated ion channels have a similar structure to VG channels but are controlled by the binding of a ligand. They can be controlled by either intracellular or extracellular ligands. Examples include Calmodulin bound to C-terminal and Cycli nucleotide binding domain.

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9
Q

What do Na+ / K+ selective channels control?

A

Na+ / K+ selective channels control membrane excitability – depolarize cells.

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10
Q

What do channels with added permeability to calcium regulate?

A

Channels with added permeability to calcium directly regulate the activity of calcium-sensitive proteins.

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11
Q

What do Cl- selective channels control?

A

Cl- selective channels control membrane excitability – reduce resistance/hyperpolarize cells, reduce action potential firing.

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12
Q

What is the structure of the nicotinic acetylcholine receptor (nAChR), and what is its function?

A

The nicotinic acetylcholine receptor (nAChR) is a cys-loop type receptor – pentameric assembly. In muscle, it is composed of five subunits (αβ𝛾ε). Each has four TMs (M1, M2, M3, M4) with a large external-facing N domain and an intracellular loop between M3 and M4. M2 lines the pore.

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13
Q

What is the significance of multiple subunits in any one ligand-gated ion channel family?

A

Multiple subunits exist within any one ligand-gated ion channels family. Different subunit combinations make up receptors in different parts of the brain. This complexity provides diversity and an opportunity for drug targeting. For example, nAChα4 is involved in reward pathways and nicotine addiction.

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14
Q

How do neuronal nAChRs differ in composition and affinity?

A

Neuronal nAChRs exist as α2 - 10 & β2 - 4 and each has a different affinity depending on composition and location. The α4β2 subtype, which is abundantly expressed in the cortex and hippocampus, has high affinity to agonists nicotine and varenicline. Other subtypes have different affinities for various agonists and are found in different parts of the brain.

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