Ion Channels Flashcards
What term describes how fast ions go through an open channel?
Permeation
What are the relative intra and extracellular ion concentrations for Na+, K+, Ca2+ and Cl-? (in mM)
In Out Na+ 10 145 K+ 120 4.5 Ca2+ .0001 1.0 Cl- 20 116
Ions higher outside expect K+ (higher inside)
Also more [A-] protein inside
What are key components of ion channels?
External surface glycosylated Selectivity filter Inner vestibule Gate Sensor (pore +)
How do ion selectivity filters work?
Ion binds at selectivity filter, and the large aqueous cavity and negative dipole of the pore helices enable fast ion permeation
How is a typical K+ channel gated?
Voltage gated
Membrane depolarization opens gate
Repolarization causes it to close
What are the different states of the Na+channel?
Open with membrane depolarizes Closes and inactivates (blocked) Membrane repolarization Becomes unblocked (resting) Ready to open again when membrane depolarizes again
What are some different stimuli that ion channels can respond to, and what effects can these signals have in the cell?
Stimuli: Electrical (action potential) Chemical (ligands, Ca2+, nucleotides, ATP, lipids, etc.) Mechanical (force, volume, osmolarity) Light Temperature (heat/cold)
Effects:
Electrical Signal
Chemical signals (Ca2+)
These lead to cellular responses
What effects can an influx of Ca2+ have on the cell?
Muscle contraction
Hormone secretion
Neurotransmitter release
Synaptic plasticity
Other than the plasma membrane, where else can you find ion channels?
Membranes of intracellular organelles (ER, Mitochondria)
How do we sense the heat of chili peppers and the cool of peppermint?
Transient Receptor Potential (TRP) channels
Hot and cold sensing neurons
(As well as chemicals - capsaicin from chili, menthol from mint)
How do BK channels regulate vesicular tone?
Agonist leads to Ca2+ release in cell Depolarization opens Ca2+ voltage gated channel, Ca2+ influx Ca2+ increase opens BK channels Efflux of K+ causes hyperpolarization K+ inhibits Ca2+volt channel Reduced Ca2+ signaling cascades
What are the two types of light sensitive ion channels?
Channelrhodopsins
On: ChR2 sensitive to blue light
Efflux of K+, influx of Na+ and Ca2+
Off: NpHR sensitive to yellow light
Influx of Cl-
Can control channel activity with light using channelrhodopsins (optogenetics) to cure blindness
What are examples of bioelectricity used for diagnosis?
ECG
EEG
What is required for the establishment of the membrane potential?
- ) Lipid bilayer (2 compartments)
- ) symmetric distribution of ions across the plasma membrane (ion gradient)
- ) Selective ion channels in the plasma membrane
What are the components of bilayers, ion gradients, and ion channels in terms of electricity?
Bilayer = capacitor
Ion gradient = battery
Channel = resistor (conductor)
What are the requirements for equilibrium potential of an ion?
- ) Concentration gradient of an ion
- ) Presence of the ion-specific channel
The net efflux of K+ out of the cell results in a charge separation across the membrane. This establishes an electrochemical equilibrium in which the free energy of the K+ gradient is balanced by the membrane potential (voltage) established by charge separation.
How do you calculate Equilibrium potential of a particular ion?
Nernst equation At equilibrium (no net ion flux =0) , free energy due to concentration gradient = electrical energy due to charge separation (membrane potential)
Vx = RT/zF ln ([X]o/[X]i)
= 58/z log10 ([X]o/[X]i)
z= valence of ion
What determines which direction ions glow through a channel?
Equilibrium potenital
What usually sets the resting membrane potential?
K+ leak channels
Under resting conditions, K+ permeability is much higher than Na+ because of K+ leak channels
Resting membrane potential (Vm) is closer to equilibrium potential for K+
How are leak channels different from voltage gated or ligand gated ion channels?
Leak channels are open almost all the time
What are the limits of the Nernst equation?
- ) Cannot be used to calculate effect of having a mix of K+, Na+, and Cl- channels open.
- ) Cannot be used to calculate effect of time-dependent changes in channel conductance.
___________ refers to the ease with which ions cross the membrane, and is directly proportional to the total number of open channels for a given ion in the membrane.
Permeability
How does the Goldman-Hodgkin-Katz (GHK) Equation calculate membrane potential?
The membrane potential is a weighted average of the membrane conductivity of all ions (multiple channels taken into account).
Changes in conductance over time are reflected in changes in the membrane potential.
Equation reduces to the Nernst equation, fi the conductance of one ion is much less than the others.
Equilibrium values derived from Nernst equation are important because:
- ) they determine whether opening ion channels will be excitatory or inhibitory
- ) during an action potential, the membrane potential transitions between the Na+ and K+ equilibrium values
What is the effect of increasing or decreasing conductance to a specific ion during an action potential?
Opening of an ion channel will cause ion flux that changes membrane potential towards that ions equilibrium potential
Hyper polarization - opening of K channels (efflux)
Depolarization - opening of Na channels (influx)
What are the two classes of time-dependent changes in membrane potentials?
Graded potenital - characterized by conduction with decrement
Action potentials - exhibit rapid “all or none” conduction - can have lon propagation
How do graded potentials work?
NT binds ligand-gated ion channels (ionotropic receptor)
Na+ enters cell through opens channels
Current spreads
The strength of the signal decreases with distance
How are action potentials triggered?
Action potentials are generated if summed graded potentials reach a threshold
Generated by synergistic actions of voltage-depdendent ion channels
(If gap is too long - no AP)
Na channel activation (influx) triggers depolarization
K channel activation (efflux) triggers repolarization and hyperpolarization
Contrast graded and action potentials.
Graded potentials
- caused by ion channels that cause excitatory or inhibitory changes in membrane potential (can result from ionotropic or metabotropic receptors)
- vary in duration and magnitude
- decreases with distance
- occur in dendrites and cell body
Action potenitals
- caused by sequential activation of voltage-gated Na+ and K+ channels (require a threshold depolarization to initiate)
- always the same duration and magnitude
- propagates without decrement
- initiate in axon hillock and propagate along the axon
What are the three states of voltage-gated sodium channels?
- Closed
- Open
- Inactivated (refractory period)
How do voltage sensors in voltage-gated Na+ channels enable positive feedback?
Hyperpolarized (and resting) - most channels closed
Depolarized (when graded potential reaches threshold) - some channels are open
**Na+ influx makes the membrane more depolarized
More depolarized - most channels are open
As channels begin to inactive (and eq. Na mem. potential is approaches, the potential peaks)
What leads to repolarization during an action potential?
- increasing activation of voltage-gated Na channels
- opening of delayed voltage-gated K+ channels
(return to resting)
*Ion channel selectivity and gating properties are critical for AP generation
Why can the spreading membrane potential change only be propagated in one direction?
Refractory period
- inactivation of Na+ channels
*Action potential only moves in one direction
What is saltatory conduction?
using myelin insulation to lower the membrane capacity, prevent leakage, and maintain threshold for a greater distance
How can the transmission of voltage spike (action potential) be increased?
- ) Decreasing the axial resistance of the axon (larger diameter since R is inversely proportional to area)
- ) Reducing the capacitance of the membrane (coating the axon in a highly insulating later - myelin sheath)
What is the affect of increased axonal diameter and myelination on conduction velocity?
Increases
Able to go further
What are the roles of the dendrites, cell body, and axon?
Dendrites collect electrical signals
Cell body integrates incoming signals and generates outgoing signal to axon
Axon passes electrical signals to dendrites of another cell or to an effector cell
What is an electrical synapse?
Gap junction channel between neurons
Bidirectional
Found in heart
Which channels at chemical synapses are responsible for the conversion of electrical signals to chemical signals?
Voltage gated calcium channels
Action potential (depolarization) triggers Ca2+ influx through channel Ca2+ allow NT release Also important for muscle contraction at the neuromuscular junction (action potential triggers release of Ca2+ from sarcoplasmic reticulum)
How is the KATP channel involved in insulin secretion?
ATP gated K+ channel
ATP inhibits current
Low glucose, low ATP, channel active, K+ efflux
High glucose, high ATP, channel inhibited, no K+ efflux, membrane depolarization, triggers Ca2+ influx, allows for insulin secretion
How can Channelopathy associated insensitivity to pain occur?
Mutation in voltage-gated sodium channel
Loss of function mutation in pain sensing neurons
How might an antibody be used for pain and itch relief?
Use a monoclonal Ab to target and inhibit pain sensing neuron voltage gated sodium channel
What causes GEPD (generalized epilepsy with paroxysmal dyskinesia)
BK channelopathy
Gain of function mutation of BK channel
(mutation in Ca2+ binding site involved in regulation - makes channel more sensitive)
