14 - Ion Channels Flashcards

1
Q

Which ion concentrations are HIGHER INSIDE?

intracellular

A

K+

potassium

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2
Q

Types of Gated Ion Channels

A

Voltage-Gated

Respond to changes across membranes

Ligand-Gated

Either extracellular or intracellular ligand

Mechanicaly Gated

hair or hearing, we dont discuss

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3
Q

Activated Neuromuscular Junction Steps

A

After Nerve Impulse

  1. Pre-synaptic Voltage gated Ca2+ Channel OPENS
    1. allows for Ca2+ to release acetylcholine
  2. ACThbindsPost-synaptic ACTH gated cation channel
    1. allows Na+ to enter the muscle cell
  3. Post-Synaptic Voltage-Gated Na+ Channel
    1. also lets Na+ enter the muscle cell
  4. Ca2+ Gated Release channel
    1. releases Ca2+ from muscle’s sarcoplasmic reticulum
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4
Q

Describe how ion-transporters / pumps establish

electrochemical gradients + voltage potentials

across a membrane

A

Cell / Organelle membranes are barriers to charged ions

  • Ion Transporters/pumps push ions against their gradient
    • Imbalance of ions across the membranes
      • lead to ELECTROCHEMICAL GRADIENTS
        • = Chemical + Electrical (gradient)
  • Difference in BOTH solute concentation & charge
    • across the membrane
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5
Q

INHIBITORY

Transmitter gated ion channels

A

CHLORINE

GABA- Gated Cl- Channels

glycine-gated Cl- Channels

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6
Q

Ion Channels Selectivity

A

Some ion channels are:

HIGHLY SELECTIVE & VERY SPECIFIC

only allow the transport of 1 specific ION, interact with side chains

Some ion channels allow for transport of VARIOUS ions

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7
Q

GABA-B Function

EXCITORY for what ion channels?

A

GPCR that regulates ion channels

K (out) channel

lets K+ leave membrane

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8
Q

Acetylcholine Receptor

(AChRs)

2 Types

A

5 Subunits in a ligand-gated channel

(2*Alpha - Beta - Delta - Gamma*middle)

2 primary types of AChRs

Nicotinic

Muscarinic

muscarine is much more POTENT = TOXIN, locks the channel

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9
Q

Photo of an action potential illustrating the rise and fall of membrane potential over time

A

PROPAGATION GOES TO THE RIGHT

but the order action potential wave order is to the left

Closed -> Open -> Inactivated –> repeat

STIMULUS -> Depolarized -> Repolarized

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10
Q

Three States of Ion Channels

A

Closed -> OPEN -> Inactive

-Polarized- (negative inside)

Closed

+DEpolarized+ (positive inside):

OPEN -> Inactive

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11
Q

Describe how ion-transporters / pumps

establish ion gradients

A

P-Type Pump

also F-Type/V-type Proton pump & ABC Transporter

  • ATP phosphorylation -> Conformational change
    • allows to push IONS against the gradient
  • Ex. 3Na+ / 2K+ Antiporter
    • Na OUT
      • typically high outside, so against its gradient
    • K IN
      • typically high INSIDE, so also against its gradient
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12
Q

Uniport

A

Equal transport of

ONE molecule

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13
Q

Antiport

(type of coupled Transport)

A

2 molecules in the OPPOSITE DIRECTION

1 = transported molecule

1 = CO-Transported ION

Ex. 3Na/2K antiporter

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14
Q

Electrochemical Gradient

A

Chemical + Electrical Gradient

  • Chemical:
    • difference in solute concentration across a membrane
  • Electrical:
    • difference in charge across a membrane.
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15
Q

Describe how 3 activity states of voltage-gated ion channels propagates an ACTION POTENTIAL

A

​​Closed -> OPEN -> Inactive

(Voltage-gated Na+ channels)

  • STIMULUS –> leads to DEpolarization
    • Closed –> OPEN
      • +ions+ are allowed to flow inside
      • Action Potential propegated –> RIGHT
  • ​​​OPEN –> Inactive channel
    • Keeps from action potential from pushing LEFT
      • allows for the ion pumps to, re-establish the potential
        • inside returns to -negative-
          • ​= -Repolarization - Channel Closed
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16
Q

Symport

(type of coupled Transport)

A

EQUAL transport (same direction)

of 2 Molecules

1 transported + 1 Co-transported ion

17
Q

GABA-B Function

INHIBITORY for what ion channels?

A

GPCR that regulates ion channels

Calcium (IN) Channel

keeps Ca from entering cell

Adenyl Cyclase

inhibits AC from creating cAMP

18
Q

Na+ / K+ Antiporter Steps

A
  1. Na+ Loads
    1. Hydrolysis of ATP -> Phosphorylation of PUMP
      1. Conformational Change
  2. Release of ADP leads to another Conformational Change
    1. Allows for binding of = K loads
      1. Na+ OUT leaves cell
  3. Phosphate is hydrolyzed
    1. -> Conformational change
  4. K+ IN enters cell
    1. ​REPEAT
19
Q

What is one drug that targets ion channels and alters their ability to respond to ligands or work as partial agonist to modulate channel activity

A

Varenicline (Chantix)

  • partial agonist of one subtype of:
    • Nicotinic Acetylcholine Receptor
      • ​membrane-bound ligend-gated ion channel Na/K

Barbs / Steroids / BZD

+Agonist of GABAA Ion-Gated Channel

increases the influx of Cl- –> inhibits firing of action potential

20
Q

GABA-A Antagonist

Types / Function

A

Stimulant Effect / Cause Convulsions

can be used to counteract large doses of Barbituates

PICROTOXIN

21
Q

Understand that action potentials lead to release of neurotransmitters, like acetylcholine, at a

synapse, and realize that neurotransmitters are ligands whose receptors are ion channels in the post-synaptic cell.

A
  • Action Potential propegated –> nerve terminal (SYNAPSE)
    • NT = Acetylcholine RELEASED from synaptic vesicles
      • ACTh -> synaptic cleft
        • ACTh targets Transmitter gated ion channel
          • ALLOWS FOR AP TO BE PROPEGATED TO THE NEXT AXON
22
Q

3 States of Ligand-Gated Ion Channels

A

Occupied & Closed

(inactive until degraed or ligand is removed)

vvvvvv

Unoccupied & Closed

^V^V^(both ways)V^V^

Occupied & OPEN

23
Q

P-Type Pumps

A

Maintain Ion Gradients & Require ATP

  • ​Phosphorylated by ATP
    • -> conformational change
      • allows for ions to move against the ion gradient
        • Na+ / Ca2+
        • K+ / H+
24
Q

y-Aminobutyric Acid

GABA

A

Inhibitory NT in CNS

Has 2 receptors:

GABAA, TYPE-A = Cl- Channel linked receptor

GABA<span>B</span>, Type B = GPCR that regulates ion channel

25
Q

EXCITATORY

Transmitter-gated Ion Channels

A

GAS

Glutamiate-gated Ca2+ Channels

Acetylcholine-gated Cation Channels

Serotonin-Gated cation Channels

26
Q

GABA-A Agonist

Types & Function

A

SEDATIVE / ANXIETY RELIEF

Cl- influx -> ​inhibition of firing new AP’s

Barbiturates

Steroids

Benzodiazepines

27
Q

Patch-Clamp Recording

A

Used to Monitor / Isolate an ION CHANNEL

uses a micropipet to detach the patch of the membrane

to see the activity of ion channels

28
Q

Ion Channel’s

Selectivity Filter & Vestibule

A

Some Ion channels are highly selective & very specific

  • Vestibule
    • Large area that has water molecules that interacts with the various ions.
  • Selectivity Filter
    • STRIPS IONS of WATER
      • only lets SPECIFIC ions pass through the channel
      • specific alignment /interaction of side chains
29
Q

Na+ / K+ Antiporter

steps / function

A

3Na+ OUT Na is typically HIGH outside

2K+ IN K is typically low outside / high inside

(Against their chemical gradients)

to form ION GRADIENT

Conformational Change

30
Q

Where are most ion channels located?

A

NODES OF RANVIER

Gaps between Glial Cells (schwann cells in PNS)

(insulation, sections of layers of myelin sheath)

31
Q

Which ions are HIGHER OUTSIDE the Cell?

extracellular

A

Cations

Ca2+ > Na2+

(10,000x > 10-30x)

Anions:

Cl-

32
Q

PSP

A

Post-Synaptic Potential

Frequency of AP’s depend on

STRENGTH OF SIGNAL

might need to reach a THRESHOLD for magnitude to occur

monitored by PATCH CLAMP

33
Q

GABA-A Function

A

Cl- Channel-Linked Receptor

Influx of Cl- -> INHIBITS firing of new AP’s

Agonist produce sedative effects / relieve anxiety

BARBS / ​steroids / BZD

Antagonist -> stimulant / convulsant

Picrotoxin