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39 Cards in this Set
- Front
- Back
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Voltage-gated ion channels
a. Sensitive to...? b. Selective for...? c. Examples |
a. Membrane potential
b. highly selective for particular ions c. Na, Ca, K, Cl channels |
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What are 2 classes of ligand-gated channels?
What are examples of each? |
Extracellular ligand binding
-non-selective cation channels -anion selective Intracellular sensor -Ca-activated K channel |
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What can be measured using the patch-clamp method?
What variable is controlled exogenously? |
Ionic current flow through a channel
Membrane voltage is controlled |
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What is the scale of the current flow ?
Timescale of open/closed fluctuation of channels? |
a few picoamperes (10^-12)
milliseconds to seconds |
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How fast do ions move through an open ion channel?
How does this prove the channels are aqueous pores? |
6 million ions per second
This is too fast for a pump or carrier |
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What is permeation?
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Speed of ions flowing through a channel
~10^7 to 10^8 ions/sec |
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What type of channels are generally selective?
Non-selective? |
Voltage-gated = selective
Ligand-gated = non-selective |
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How does a K channel optimally move K ions without moving Na ions?
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Optimal fit formed between the carbonyl oxygens facing the pore of the channel and the K ion
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What is the reversal potential?
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The membrane voltage at which the net current through the channel = 0
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How does Erev determine whether a channel is excitatory or inhibitory?
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Excitatory: Erev > V threshold
Inhibitory: Erev < V threshold |
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What factors determine Erev? (2)
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Selectivity of the channel
Concentration of ions |
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Why is Erev for a K channel different from Ek?
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Because K channels a very slightly permeable to Na
Erev is slightly depolarized (closer to ENa) |
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What does the magnitude of current through an open pore depend on...
a. Theoretically? b. Practically? c. Exception to b |
a. Membrane potential
-permeability of channel for a given ion -concentration gradient, valence of ion b. Membrane potential c. Ca (large conc. gradient --> non-linear current-voltage relationship) |
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What is gating?
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The instantaneous transition between open and closed states of an ion channel
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What favors channel opening?
How does this factor affect channel opening kinetics? |
Depolarization favors channel opening
Larger depolarization --> faster channel opening |
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How do you measure the voltage dependence of an ion channel?
What does the slope of this relationship represent? |
Open probability, Popen(V)
Slope = the amount of charge in the voltage-sensing mechanism of the channel |
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What are the effects of larger depolarizations on opening of ion channels?
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Larger depolarization -->
Quicker activation of channel Steady state open probability is higher |
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What is the difference between the inactive state and the closed state of a channel?
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Inactive = non-conducting, cannot be opened
Closed = non-conducting, can be opened |
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What is the relationship that defines the current in a system with many channels?
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I = (N)(Popen)(i)
current = (# channels)(open prob.)(current through a single channel) |
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What is the principal subunit of a voltage-gated ion channel? (2 types)
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1. Tetramer of identical subunit (K)
2. Pseudotetramer of homologous repeats within a single polypeptide (Na, Ca) |
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What makes up the subunits of the channels? (2 things)
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1. 6 transmembrane spanning segments
2. Pore region (p-region) |
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Where is the voltage-sensor and what is it comprised of?
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On S4 segment
Contains alternating sequence hydrophobic and pos. charged aa Lys or Arg every 3rd aa |
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How are K channels inactivated?
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Cytoplasmic amino terminus plugs open channel
(ball and chain) |
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How are Na channels inactivated?
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Cytoplasmic linker between S3 and S4 swings over to occlude open pore (hinged lid)
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What are consensus sites?
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Sites on cytoplasmic domain of channel for phosphyorylation by PKC or PKA --> channel regulation
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What is the general structure of all voltage-gated ion channels?
What are the roles of accessory subunits? |
Principal tetrameric pore --> a-subunit
Accessory subunits that modulate gating, localization of ion channels |
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K channels
a. selectivity? b. role? |
a. Highly selective Erev-->Ek
b. Hyperpolarize |
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Na channels
a. selectivity? b. role? |
a. Moderately selective Erev near ENa
b. Depolarization |
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Ca channels
a. selectivity? b. role? |
a. Highly selective
b. Depolarizes cell (Erev pos.), second messenger |
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Cl channels
a. selectivity? b. role? |
a. Selective, but Erev varies
b. Inhibitory effect |
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Antiepileptic drug
a. Example drug b. Mechanism |
a. Dilantin
b. Use-dependent block of Na channel |
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Analgesic
a. Example drug b. Mechanism |
a. Mexiletine
b. Use-dependent block of Na channel |
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Antiarrhythmia
a. Example drug b. Mechanism |
a. Fleccainide
b. Use-dependent block of Na channel |
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Antihypertensive
a. Example drug b. Mechanism |
a. Nimodipine
Diazoxide b. Use-dependent block of L-type Ca channel ATP-dependent K channel opener |
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Anxiolytic
a. Example drug b. Mechanism |
a. Xanax
b. Enhances GABA receptor activity |
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Antidiabetic
a. Example drug b. Mechanism |
a. Tolbutamide
b. Blocks ATP-dependent K channel Increase insulin secretion by b-cells |
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What is a use-dependent block?
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Drug block is weak for quiescent cells, stronger for active cells
Due to voltage-dependent conformational changes in channel, i.e. drug has more affinity to conformation at depolarized potentials |
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What happens in Myasthenia gravis?
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Immune-mediated block and downregulation of nicotinic AchR
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What happens in paralytic shellfish poisoning?
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Block of Na channels by saxitoxin
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