Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

PMCOL 371 - Cellular Neuroscience > 5- Molecular aspects of Na and K channels > Flashcards

5- Molecular aspects of Na and K channels Flashcards

1
Q

Ion channels can be grouped according to _____, ______ and ________

A

Ion channels can be grouped according to properties, pharmacology and sequence homology

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Voltage-gated Na+ channels are highly selective for ______

Activate rapidly upon _______

Inactivate rapidly at ______

A
  • Voltage-gated Na+ channels are highly selective for sodium ions
  • Activate rapidly upon depolarization (AP upstroke)
    • positive feedback process
  • Inactivate rapidly at positive membrane potentials
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Recovery from inactivation requires ________

A

Recovery from inactivation requires repolarization of the membrane potential (back to resting MP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What fish/amphibian toxin(s) target voltage gated Na+ channels?

A
  • Tetrodotoxin, TTX (puffer fish)
    • highly selective for neuronal and skeletal muscle Na+ channels
    • inhibitor
  • Batrachotoxin (arrow poison frogs)
    • activator
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Why would Na+ channel inhibitors be used clinically?

A

Local anesthetics and anti-arrhythmics

eg: Lidocaine
* inhibit rapid firing of Na+ in sensory neurons (frequency dependent)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

_____ from anemonia sulcata is a voltage-gated Na+ channel activator that opens neuronal and muscular Nav channels

A

ATX II from anemonia sulcata is a voltage-gated Na+ channel activator that opens neuronal and muscular Nav channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How can both Na channel inhibitors and activators lead to rapid paralysis?

A

Correct neuronal and muscle conduction/contraction relies on proper AP firing

Toxins can either stop AP from firing (inhibit) or prevent it from firing again (activators - na+ needs to recover)

  • Na channel inhibitors prevent channels from opening = no AP (eg TTX)
  • Na channel activators prevent channels from inactivating = no repolarization = No AP’s (eg ATX II)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the structure of Sodium channels?

A
  • Alpha subunit
    • encoded by SCNxA gene
    • One polypeptide with 4 similar domains each with 6 membrane spanning regions
    • Selectivity filter between 5 and 6 of each domain
    • “Hinged lid” inactivation gate between 6 of third domain and 1 of 4th domain
      • DIII-DIV interface (IFM)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What toxins act on site 1 of the sodium channel?

A

TTX, STX, u-conotoxins

Site 1 = on selectivity filter of first domain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What toxins act on Site 5 of Na channels?

A

Brevetoxins

Ciguatoxins

Site 5 is on 6th membrane spanning region of domain I

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What toxins act on site 4 of Na channel?

A

Site four between 3rd and 4th membrane spanning region of domain II

Scorpion-beta-toxins

Spider beta-toxins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What toxins act on Site 2 of Na Channels?

A

Site 2 = on 6th membrane spanning region of Domain III

Batrachotoxins

Grayanotoxins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What toxins act on site 3 of Na channels?

A

Scorpion alpha-toxins

Sea anemone toxins

Site three = in btween 3rd and 4th membrane spanning regions of Domain IV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the three major types of potassium channel?

A
  1. Voltage gated
  2. Calcium activated
  3. Inward rectifier
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which potassium channels contribute to slow recovery following AP?

A

Voltage-gated K channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Which potassium channels are active after polarization?

A

Calcium-activated K channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Which potassium channels are in charge of maintaining the resting membrane potential?

A

Inward rectifier k+ channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Two types of voltage gated K channels:

A
  • Delayed rectifiers
    • Kv1.x to 6.x
  • Calcium activators
    • BK, IK, SK
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Three types of inward rectifying potassium channels:

A
  • IRK1
    • Kir1.x, 2.x, 4.x and 5.x
  • GIRK
    • Kir3.x and CIR
  • KATP
    • Kir6.x plus SURx
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Why are there so many types of K channels when compared to Na Channels?

A

The duration of the AP and the RMP are really important in controlling cellular excitability

K channels control both

Lots of K channels to “fine tune” excitability

In contrast, the role of Na channels is mostly limited to initiating the upstroke of the AP only

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How does potassium channel activation/inactivation compare to Na channels?

A

K+ channels activate and inactivate more slowly than Na channels upon depolarization

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Three blockers of K channels:

A
  • Tetra-ethyl-ammonium (TEA)
  • Dendrotoxin
  • Agitoxin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Big/Intermediate Calcium activated K+ channels:

Called: _____ or _____

  • respond to ______
  • Sensitive to _______
  • Blocked by: _______, ______, ______
A

Calcium activated K+ channels:

Called: BK/IK or K<u>Ca</u>

  • respond to voltage (ie voltage-dependent
  • Sensitive to micromolar internal calcium
  • Blocked by: TEA, ChTX and IbTX (scorpion venom, buthus sp.)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the physiological roles of BK/IK or KCa calcium-activated K+ channels?

A

Repolarization of excitable cells

eg smooth muscle and beta-cells (insulin secretory response)

25
What are SK channels? Sensitive to? Physiological role?
* Small conductance calcium-activated K+ channels * Sensitive to apamin (bee venom) * Controls after potential and AP duration * “shape of AP”
26
What modifies K+ channel gating (Voltage dependent (Kv) K+ channels)
beta-subunit modifies K+ channel gating eg Kvbeta or mink
27
There are 11+ Kv channel families; each contains \_\_\_\_\_\_\_ Subunits co-assemble as ____ to form \_\_\_\_\_\_
There are 11+ Kv channel families; each contains several homologues (eg Kv1.1-Kv1.7) Subunits co-assemble as _tetramers_ to form _functional channels_ \*only subunits from the same family can co-assemble
28
Compare Kv channel assembly to Nav channels
Kv channel assembly: 4 polypeptide subunits co-assemble to form the major alpha subunit tetramer with the major properties of the Kv channel Only 1 polypeptide subunit is required for Nav channels
29
What effect do Kv channel inhibitors have?
Kv channel inhibitors favor depolarization = increasing excitability and AP firing rate
30
What effect do Kv channel activators have?
Kv channel activators favor repolarization = decreasing excitability and AP firing rate
31
What is the effect of hypo-active neurons?
* Decreased frequency of AP firing * CNS depression, neuronal-conduction disorders (eg multiple sclerosis) and cognition disorders
32
What is the effect of hyper-active neurons?
* Increased frequency of AP firing * CNS hyperexcitability, seizures, pain, ADHD, anxiety, bipolar disorder and schizophrenia
33
What are the physiological roles of strong inward rectifier K channels?
* Kir2,4,5.x * Clamp membrane potential near Ek * Allow small efflux of K ions positive to Ek * Stabilizes neuronal membrane potential
34
Properties of Strong inward rectifier K channels: * Open probability compared to voltage? * Current flow? * Strong inward rectification caused by internal block by \_\_\_\_\_\_
Properties of Strong inward rectifier K channels: * Open probability **independent of voltage** (*no S4 segment*) * Current flow **passively dependent on direction of K ion flow (ie Ek)** * Strong inward rectification caused by internal block by _polyamines and Mg++ ions_
35
Weak inward rectifier K channels are always \_\_\_\_\_\_ When open, they have what physiological role:
Weak inward rectifier K channels are always _gated_ (usually closed and require activation) When open, they: * clamp membrane potential near Ek and affect the AP shape * Allow larger efflux of K ions pos to Ek (when compared to strong IRKs)
36
Properties of weak inward rectifier K channels: * Open probability vs voltage? * Current flow? * weak inward rectification caused by:
Properties of weak inward rectifier K channels: * Open probability **independent of voltage** (*no S4 segment*) * Current flow **passively dependent on direction of K ion flow** (ie Ek) * weak inward rectification caused by **a reduced internal block by polyamines and Mg++ ions** (compared to strong IRKs)
37
Weak IRKs influence the ____ and the _____ (of the AP)
Weak IRKs influence the _membrane potential_ and _most of the AP_
38
Strong IRKs influence the ______ and _____ (of the AP)
Strong IRKs ONLY influence the _resting membrane potential_ and _the “foot” of the AP_
39
The IKACh channel is formed by a \_\_\_\_\_\_\_\_ Activated by ______ and \_\_\_\_\_
The IKACh channel is formed by a _heterotetramer of Kir3.1 and 3.4 (CIR)_ Activated by _membrane delimited G-protein activation coupled to muscarinic receptors_ and _acetylcholine and analogs_
40
Provide an example of physiological role of IKACh channel?
IKACh is a weak inward rectifier K channel activated by ACh and analogs * Found in high density in the SA node, AV node and atrium of the heart. VAGAL nerve stimulation slows heart rate by releasing ACh at the neuromuscular junction and activating the IKACh channels
41
What is KATP?
ATP sensitive K channel * Found in many different tissues and primarily **inhibited by ATP** * ⤓ATP (⤓glucose) ⇒ ⤒ K channel
42
The ATP-sensitive K channel has rich pharmacology because of the ________ receptor
The ATP-sensitive K channel has rich pharmacology because of the _sulphonylurea_ receptor (SUR)
43
What are 7 physiological roles of ATP-sensitive K channels (KATP)?
* Repolarization of cardiac AP in hypoxia/ischemia * Cardioprotective * Control of glucose/insulin secretion * Control of smooth muscle tone * Myoprotection during skeletal muscle fatigue * CNS protection during ischemia (eg stroke) * Found in “energy-sensing” neurons in the hypothalamus INHIBITED BY SULPHONYLREAS
44
What is the subunit assembly of strong inward rectifier K+ channels (IK1)
IK1 is a homotetramer
45
Subunit assembly of IKACh?
Heterotetramer * passive gating
46
Subunit assembly of KATP inward rectifier K+ channels
Hetero-octomer Sulphonylrea receptor Nucleotide binding folds (where ATP binds)
47
What are the features of the KcsA channel? (voltage gated K+ channel solved to 3.2A resolution)
A. 4 identical subunits B. Each subunit has two transmembrane helices C. Selectivity filter D. Water-filled cavity E. Inverted “teepee” D. Gating mechanism
48
What is the purpose of the water-filled cavity in KcsA?
Helps to overcome **electrostatic destabilization** (ions don't like hydrophobic regions)
49
What are three features of the selectivity filter/ion conduction pore of KcsA? Motif? What fits? What determines selectivity?
* Signature “GYG” motif * Space for 3 K+ ions and a water molecule * The 4 tyrosine residues of the filter determine selectivity
50
Antibodies bind to ________ of KcsA channel
Antibodies bind to _extracellular loop_ of KcsA channel
51
What happens to water of hydration before ions enter selectivity filter of KcsA?
Water of hydration stripped before ions enter selectivity filter
52
How many conformational positions are there for K+ ions in the selectivity filter? (KcsA)
four Oxygen cage defines selectivity for K+ ions
53
What feature of KcsA defines selectivity for K+ ions
Oxygen cage
54
What is present on valinomycin and nonactin (antibiotic and antimycotic compounds) that allows K+ to enter bacterial and fungal cell membranes?
Oxygen cages Valinomycin and Nonactin have oxygen cages and act by allow K+ to enter bacterial and fungal cell membranes
55
What are four essential elements in the structure of K channels?
1. Plenty of water 2. Helix dipoles 3. Customized oxygen cages 4. Multiple ion occupancy
56
Which K channels are more positively charged?
BK are more positively charged than IK/SK
57
What is the importance of the helix dipoles in K channels?
Helix dipoles attract ions into the water filled cavity High [K+] relative to the outside of the channel = energy in
58
What leads to pushing ions out of the K channel?
Increased random collisions of K+ ions in filter

PMCOL 371 - Cellular Neuroscience (19 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions