voltage gated Ca channels

Question 1

What is the primary pore-forming subunit of a voltage-gated calcium channel?

Answer 1

alpha 1

Question 2

Which subunit regulates the activity, trafficking, and stabilization of the α1 subunit?

Answer 2

beta

Question 3

Which subunit is responsible for modulating channel function and ensuring its trafficking to the plasma membrane?

Answer 3

α2δ subunit

Question 4

What is the role of the γ subunit in voltage-gated calcium channels?

Answer 4

influences gating not all CaV channels have this subunit

Question 5

How many β subunit isoforms are there

Answer 5

4

Question 6

Which subunit is essential for determining the ion selectivity of the voltage-gated calcium channel?

Answer 6

a1

Question 7

What are the three main types of CaV channels?

Answer 7

L P Q N R T

Question 8

What are L-type CaV channels and where are they found?

Answer 8

(CaV1.1–CaV1.4) are high-voltage-activated channels primarily found in skeletal muscle, cardiac muscle, smooth muscle, and neurons. They are important for excitation-contraction coupling and hormonal secretion.

Question 9

What are the properties of P/Q-type CaV channels?

Answer 9

(CaV2.1) are high-voltage-activated channels found primarily in neurons, particularly at synapses, where they mediate neurotransmitter release. They are involved in synaptic transmission and are sensitive to the toxin ω-agatoxin.

Question 10

What is the function of N-type CaV channels?

Answer 10

CaV2.2) are also high-voltage-activated channels, primarily located in neurons. They are critical for neurotransmitter release and are inhibited by the toxin ω-conotoxin.

Question 11

Where are R-type CaV channels found and what is their function?

Answer 11

(CaV2.3) are high-voltage-activated channels found in neurons. They are involved in synaptic transmission and dendritic calcium signaling but are less sensitive to blockers compared to other types.

Question 12

What are T-type CaV channels and their key properties?

Answer 12

(CaV3.1–CaV3.3) are low-voltage-activated channels that generate transient calcium currents. They are important for pacemaking activity, neuronal firing, and oscillatory behavior in the heart and brain.

Question 13

Which CaV channel type is blocked by dihydropyridines?

Answer 13

L type

Question 14

What is the role of PKA in CaV channel regulation?

Answer 14

PKA, activated by cAMP, phosphorylates the CaV channel (especially L-type), increasing the open probability and enhancing calcium current, especially in the heart

Question 15

How does PKC affect CaV channels?

Answer 15

PKC can either enhance or inhibit CaV channel activity, depending on the context. It is activated by diacylglycerol (DAG) and calcium, influencing calcium currents.

Question 16

How do G proteins directly regulate CaV channels?

Answer 16

The Gβγ subunit of G proteins directly binds to the CaV channels and reduces calcium influx

Question 17

What is the role of G proteins in presynaptic inhibition?

Answer 17

G proteins reduce neurotransmitter release by inhibiting Ca²⁺ currents via direct interaction of the Gβγ subunit with N-type and P/Q-type CaV channels

Question 18

How does the Gs protein affect CaV channel activity?

Answer 18

The Gs protein activates adenylyl cyclase, increasing cAMP, which activates PKA. PKA phosphorylates CaV channels, leading to increased calcium current.

Question 19

What effect does the Gi protein have on CaV channel regulation?

Answer 19

Gi protein decreases cAMP levels, reducing PKA activity, which in turn lowers Ca²⁺ currents by preventing phosphorylation of the channel.

Question 20

Which channels are most affected by direct G protein modulation?

Answer 20

N and P/Q type

Question 21

How does PKA-mediated phosphorylation affect heart function?

Answer 21

enhances calcium influx, leading to stronger and faster contractions during sympathetic stimulation

Question 22

What are channelopathies?

Answer 22

diseases caused by mutations in ion channel genes

Question 23

What is Timothy syndrome and how is it related to CaV channels?

Answer 23

mutations in the CaV1.2 (L-type) channel, leading to prolonged depolarization in heart cells, resulting in arrhythmias, developmental delay, and autism.

Question 24

How does episodic ataxia type 2 relate to Ca²⁺ channel dysfunction?

Answer 24

mutations in the CaV2.1 (P/Q-type) channel, leading to poor coordination, ataxia episodes, and nystagmus due to defective calcium-dependent neurotransmitter release.

Question 25

What is familial hemiplegic migraine (FHM) and which CaV channel is involved?

Answer 25

mutations in the CaV2.1 (P/Q-type) channel, leading to migraine with aura, hemiparesis, and increased sensitivity to cortical spreading depression.

Question 26

How does congenital night blindness involve CaV channel mutations?

Answer 26

mutations in the CaV1.4 (L-type) channel in retinal cells, resulting in impaired photoreceptor signaling and poor vision in low light conditions.

Question 27

What are the symptoms of Lambert-Eaton myasthenic syndrome (LEMS) and its link to Ca²⁺ channels?

Answer 27

antibodies against CaV2.1 (P/Q-type) channels, impairing neurotransmitter release and causing muscle weakness and fatigue.

Question 28

What role do CaV2.2 (N-type) channels play in pain perception?

Answer 28

Drugs like gabapentinoids target these channels to reduce neuropathic pain by inhibiting neurotransmitter release.

Question 29

What are potential treatments for Ca²⁺ channel-related channelopathies?

Answer 29

calcium channel blockers, anti-epileptic drugs, gabapentinoids, or immunosuppressants

Question 30

What CaV channel mutation causes spinocerebellar ataxia type 6 (SCA6)?

Answer 30

CaV2.1

Question 31

What are Ca²⁺ channel blockers and how are they used clinically?

Answer 31

used to treat conditions like hypertension, arrhythmias, and angina by inhibiting L-type Ca²⁺ channels and reducing calcium influx in smooth and cardiac muscles.