Transporters & Ion Channels 3 Flashcards

1
Q

Sodium ion channel selectivity

A

Achieved using different selectivity filters:

  • Oxygen backbone
  • Side chains of Glu
  • Beside P-helix contains a P2 half helix
  • Short loop between P and P2 helices responsible for selectivity (same in Ca channels)

Voltage gated Sodium Channels (Nav) transports Na in a partly hydrated form

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2
Q

Calcium ion channel selectivity

A

Similar to Sodium

  • can be interchanged by simple mutation
  • Ca2+ is also transported in hydrated form
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3
Q

Voltage gated ion channels

A

structures of Kv1.2 and NavAb provide insight into voltage gated sodium ion channels

Voltage sensing domain (S1-S4) detect depolarisation/change in electric field
- arginines move in sliding mechanism promoting the movement of S5 & S6 via the S4-S5 helix

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4
Q

The Voltage Sensing Domain (VSD) causing channel to open

A

S1 to S4
- S4 contains positive residues (4x arginines) which respond to membrane potentials in a sliding helix model

VSD/S4 movement transferred to ion channel (S5-S6) via S4-S5 helix

  • Causes kinking of S6 to open channel
  • Opening/closing occurs at bottom half of protein (at the activating gate)
  • Glycine residue in S6 acts as a hinge
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5
Q

Inactivating voltage gated Na ion channels

A

A second gate spontaneously inactivates after a few ms of opening

Ball and Chain inactivating mechanism
- Uses the channel inactivating segment to block the otherwise open Na+ channel

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6
Q

Mechanoreceptors: opening ion channels from mechanical sensing

A

When closed, channel is in part of membrane that’s dipped
~~~~~~~\___x___/~~~~~~~

Upon mechanical stimulation, membrane stretches and the dip reduces allowing channel inside to open
~~~~¬—–x—–¬~~~~

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7
Q

Pain receptors

A

Use Nociceptors (noxious stimuli detected) such as TrpV1

  • Similar structure/organisation to voltage gated ion channels, despite lack of sequence homology
  • S1-S4 don’t move, S6 controls opening/closing

Primary function to stimulate immune and pain response:

  • Sensitized by other inflammatory components, leading to thermal hyperalgesia
  • Responds to: Noxious temperatures (>43C), Acidic pH, Arachidonic acid metabolites and endocannabinoids (inflammatory mediators) and Capsaicin (chili peppers)
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8
Q

Opposite receptor to TrpV1-heat detector (detects cold)

A

TrpM8 detects cold, responds to:

  • Gentle cooling (<23C)
  • Menthol, icilin, linalool, geraniol, hydroxycitronella
  • Low doses of menthol reduce threshold for cold detection
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9
Q

Co-transport by Symporters and Antiporters

A

Rely on secondary active transport (energy for active transport is acquired from transmembrane ion gradients of 1 of the 2 molecules)

  • Cotransport = transporting 2 molecules simultaneously
  • Symport = cotransport in one direction
  • Antiport = cotransport with both molecules going in opposite directions

Highly substrate specific (substrate binding pocket analogous to enzymes)

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10
Q

Symport (SGLT1) mechanism

A

Uses energy of sodium and proton gradients

  • Transports up to 3 sodium ions or protons
  • Transports a wide range of (or multiple) substrates including: organic metabolites, nutrients, toxins (export), cations or anions (e.g. Galactose)

Inward facing conformation = Na+ release (down gradient)

  • Na release changes Na binding pocket and galactose binding pocket
  • Galactose (glucose) binding affinity reduces and galactose is released
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11
Q

Bacterial Symporter homologue: Leucine Symporters (LeuT)

A

Structure in occluded state, sodium can’t bind without Leucine - ensuring coupled transport

  • Sodium bound in dehydrated form
  • One of the sodiums coordinates Leucine substrate
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12
Q

vSGLT

Sodium/glucose symporters from Vibrio parahaemolytics

A

SGLT belongs to the sodium solute symporter (SSS) family and cotransports 2 sodium with 1 D-glucose
- Shares LeuT fold (alternating access mechanism)

Releases Na+ at inward-facing conformation due to lower intracellular Na concentration (down gradient)

  • Na release changes Na and the Galactose (N64) binding pockets
  • Altered binding pocket conformation has lower affinity causing galactose release
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13
Q

Multi-drug resistance from bacterial efflux pumps

causing antibiotic resistance?

A

5 families of efflux:

1) ATP binding cassette (ABC) superfamily
2) Major Facilitator Superfamily (MFS)
3) Multidrug and Toxic-compound Extrusion Family (MATE)
4) Small Multidrug Resistance (SMR) family
5) Resistance Nodulation Division (RND) family

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14
Q

Glucose uptake in Small Intestine

A

Relies on 4 transporters:

1) Uniporter (GLUT2)
2) Secondary Active Symporter (SGLT1)
3) Primary active ATPase
4) Potassium channel

Glucose levels are high in cytoplasm due to SGLT1 cotransporter
- Uniporter GLUT22 therefore needed to transport glucose into bloodstream

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15
Q

Lowering stomach pH

A

Action by P-type K+/H+ ATPase

  • pH inside parietal cells (specialised epithelial cells) maintained by Cl-/HCO3- antiporter combined with passive CO2 diffusion across membrane
  • Cl- & K+ homeostasis maintained by non-gated ion channels
  • Net transfer of HCl into stomach (H+ and Cl- released into stomach)
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