PCOL 1-2 Voltage-Gated Ion Channels

Questions and Answers

How many members does VGIC family have?

143

Which ion channel is associated with the condition of episodic ataxia?

Kv1.1 and Cav2.1

Which ion channel is associated with the condition of paralysis?

Cav1.1 and Nav1.4

Which ion channel is associated with the condition of myotonia?

Kv1.1, Nav1.4, CLC1 Signup and view all the answers

Which ion channel is associated with the condition of seizures?

Kv7.2, Kv7.3, KCa, Nav1.1, Nav1.2, Cav, CLC2 Signup and view all the answers

Which ion channel is associated with Long QT syndrome?

Kv1.7, Mink, MIRP1, Nav1.5 Signup and view all the answers

Which subunit of VGICs can function on its own?

α subunits Signup and view all the answers

What are 2 members in the VGICs family that show the most diverse range/structure?

K+ and TRP Signup and view all the answers

Which subunit of VGICs can regulate expression levels, location, and trafficking?

β subunit Signup and view all the answers

Which ions are controlled by the aqueous pore in VGICs?

Na+, K+, and Ca2+ Signup and view all the answers

What is the selectivity of K+ channels over Na+ channels?

100-1000 fold Signup and view all the answers

What causes VGICs to open in response to changes in membrane potential?

Voltage sensor movement Signup and view all the answers

What is the mechanism behind inactivation of voltage-dependent Na+ channels?

Ball and Chain model Signup and view all the answers

What is the main use of tetrodotoxin in studying Na+ channels?

Experimental tool in vitro Signup and view all the answers

What is the mechanism of action of local anesthetics on Na+ channels?

Blocking the pore Signup and view all the answers

Which of the following is crucial for pain perception therefore this selective inhibitor can be used for the Treatment of Pain?

Nav1.7 Signup and view all the answers

Which type of channels are responsible for setting the cell's resting membrane potential?

Kv channels Signup and view all the answers

What is the main role of Kv channels in controlling the cell's rate of firing and shape of the action potential?

Decreasing firing frequency Signup and view all the answers

Which type of channels are being developed as potential anti-inflammatory drugs for various immune-related disorders?

Kv1.3 Signup and view all the answers

Which type of channels can trigger muscle contraction, neurotransmitter release, activation of second messenger systems, alteration in gene expression, and apoptosis (Cell death)?

CaV channels Signup and view all the answers

These drugs are used for the treatment of chronic pain and epilepsy. These are selective for Cav2.2 (N-Type) that regulate neurotransmitter release in sensory neurones

Gabapentin, Pregabalin Signup and view all the answers

Which ligand can activate TRPV1, the major pungent constituent of chili?

Capsaicin Signup and view all the answers

Which ion channels are involved in the influx of Na+ and Ca2+ in dorsal root ganglion neurons, resulting in membrane depolarization and pain perception?

TRP channels Signup and view all the answers

Which ion channels are inhibited by local anesthetics?

NaV channels Signup and view all the answers

What is the mechanism of inactivation for voltage-dependent Na+ channels?

Influx of +ve charge causes an intracellular domain to swing into the open pore of the channel Signup and view all the answers

When does deactivation of a channel occur?

When the membrane potential reverses back to its resting state Signup and view all the answers

What is the role of the Ball and Chain model for inactivation of channels?

Influx of +ve charge causes an intracellular domain to swing into the open pore of the channel to prevent ion flow Signup and view all the answers

Study Notes

Voltage-Gated Ion Channels (VGIC) Family

VGIC family consists of over 50 members.
Ion channels involved in various medical conditions include specific VGICs for episodic ataxia, paralysis, myotonia, seizures, and Long QT syndrome.

Ion Channels and Associated Conditions

Episodic Ataxia: Associated with K+ channels.
Paralysis: Connected to Na+ channels.
Myotonia: Related to Cl- channels.
Seizures: Linked to Na+ channels.
Long QT Syndrome: Involves K+ channels.

VGIC Subunits and Functions

Independent Function: Certain subunits can function autonomously.
Diversity: Na+ and K+ channels exhibit the most diverse range and structure within VGICs.
Regulation: Auxiliary subunits regulate expression levels, localization, and trafficking of channels.

Ionic Selectivity and Mechanisms

Aqueous pore in VGICs controls the movement of Na+, K+, and Ca2+ ions.
K+ channels exhibit high selectivity over Na+ channels, allowing K+ to pass more readily.
Changes in membrane potential cause VGICs to open, facilitating ion flow.

Inactivation and Mechanisms

Voltage-dependent Na+ channels undergo a specific mechanism of inactivation, where a segment of the protein occludes the pore.
Tetrodotoxin is primarily used to study Na+ channels by blocking them.
Local anesthetics inhibit Na+ channels by stabilizing the inactivated state.

Channel Functions and Therapeutic Targets

Specific VGICs are crucial for pain perception, making them targets for selective inhibitors in pain treatment.
Resting membrane potential is maintained by K+ channels.
Kv channels play a significant role in modulating the firing rate and action potential shape.

Emerging Therapeutics

Calcium channels (Cav2.2 / N-Type) are being explored as potential anti-inflammatory treatments for immune-related disorders.
Voltage-gated ion channels trigger muscle contraction, neurotransmitter release, and can initiate apoptosis.

TRPV1 and Pain Perception

TRPV1 Activation: The pungent component of chili, capsaicin, activates TRPV1 channels.
Sodium and calcium channels allow influx during pain perception in dorsal root ganglion neurons.
Local anesthetics act on Na+ channels to mitigate inflammation and pain.

Inactivation Dynamics

The deactivation of a channel occurs when membrane potential returns to resting state.
The "Ball and Chain" model describes the physical mechanism underlying the inactivation process of certain ion channels.

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Description

Test your knowledge on Voltage-Gated Ion Channels (VGICs) and their role in synaptic transmission. Identify different types of VGICs and understand their functions.