Ion channels Flashcards

1
Q

What stimuli control ion channels’ gating?

A
  • some channels respond to multiple stimuli
  • temperature
  • mechanical deformation
  • membrane potential
  • extracellular chemicals (taste, olfaction, neurotransmitters)
  • intracellular second messangers (ATP, cAMP, Ca2+)
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2
Q

Voltage gated channels of the Kv, Nav, and Cav families have _____ membrane spanning domains, each with ______ alpha helices.

A

four membrane spanning domains; six alpha helices (S1 - S6)

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3
Q

What structures do the Nav and Cav channels contain?

A
  • the four domains are linked into a single polypeptide
  • S4 helices have positively charged residues (lys or arg) at every third position (sense voltage)
  • S5 and S6 helices and the “P loop” (connects them) form the ion conducting pathway
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4
Q

What are ionotropic receptors?

A

neurotransmitter receptors are directly coupled to ion channels

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5
Q

What are pentameric ligand gated channels?

A
  • ionotropic receptor
  • lys-loop family of neurotransmitter receptor channels (GABAaRs, GlyRs, etc)
  • heteropentamers
  • each subunit has four transmembrane alpha helices (M1 and M4)
  • M2 assembles around the central, ion-conducting pathway
  • channels are selective for permeation of chloride, or allow both sodium and potassium
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6
Q

CLC chloride channels

A
  • has an ion permeation pathway
  • each permeation pathway can gate open and closed independently of one another
  • some in this family are H+/Cl- exchangers
  • important for stabilizing the resting membrane potential
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7
Q

Aquaporin water channels

A
  • tetramers where each subunit contains a permeation pathway for water molecules
  • anti-ion channels since they exclude all ions including protons
  • e.g. in kidney
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8
Q

Which channels are selective? (Kv, Cav, Nav)

A

Kv and Cav are selective. Nav is moderately selective

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9
Q

How is charge important for what passes through a channel?

A
  • channels are cation or anion selective

- ionic valence is also important

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10
Q

How are ions dehydrated in order to pass through a channel pore?

A
  • ion is stabilized within the pore by energetic interactions with the amino acids forming the pore (but not completely or they would get stuck)
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11
Q

What is one factor that can increase channel pore selectivity?

A

if an ion interacts with multiple sites while traversing the channel pore

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12
Q

Describe the gating for Kv.

A
  • the activation gate (intracellular side) can rotate around a center pivot point
  • rotation is controlled by a “voltage-sensing” charge
  • closed when cell has negative potential (deactivation)
  • open when the inside is made positive causing K+ ions to flow out of the cell (called activation)
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13
Q

Describe Nav’s activation gate.

A
  • on intracellular side
  • closed at negative potentials
  • open when the cell becomes positive and Na+ flows in
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14
Q

Describe Nav’s deactivation gate.

A
  • on intracellular side
  • open at resting potential (activation gate occludes access to a site within the inner end of the pore at which the inactivation gate can bind)
  • after the activation gate opens, the inactivation gate closes (called inactivation)
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15
Q

Describe the selectivity filter for Kv and Nav.

A

occurs within a central, ion conducting pathway formed by the four Kv subunits or four repeats of Nav (central pathway surrounded by S5 and S6 helices and connecting P loop)

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16
Q

What performs the voltage sensing for Kv?

A

the S4 helices

17
Q

What forms the inactivation gate of Nav channels?

A

cytoplasmic loop connecting repeats III and IV

18
Q

Why do many channel modifying reagents have access to their sites of action only from one site of the membrane?

A
  • the location of the selectivity filter near the extracellular side
  • the vestibule nearer the intracellular side of the Kv/Nav channels
  • the location of the activation/inactivation gates near the intracellular side
19
Q

Where does tetrodoxin (TTX) bind to Nav?

A

The entrance of the pore above the Nav selectivity filter

20
Q

Where does lidocaine bind to Nav?

A
  • must block the channel fro the intracellular side but protonated form cannot cross the membrane
  • requires the activation gate to open and the inactivation gate not to be closed to enter
  • thus the nerves with more activity are blocked first/preferentially