Cardiac Electrophysiology I Flashcards
Define Equilibrium Potential
the voltage obtained for a given concentration gradient of a single ion at equilibrium across a semi-permeable membrane
What is a Gibbs-Donnan equilibrium?
an equilibrium involving impermeable polyelectrolyte on one side of a membrane that is permeable to salts but impermeable to the polyelectrolyte. Results in an unequal distribution of salts across the membrane potential that has the same sign as the charge on the polyelectrolyte
What is a diffusion potential?
It occurs when two or more ions are permeable to a membrane but the different ions have differing permeabilities
How do you calculate diffusion potentials?
Goldman- Hodgkin- Katz equation.
This equation describes the independent gradients and electrical forces.
What is an example of a diffusion potential?
Cell resting potential and action potential
What can you use to calculate equilibrium potential?
Nernst equation can give equilibrium potential for a specific ion
Describe the general structure of volt gated ion channels
Channel is specific for individual ions and is typically a tetrameric structure. Each subunit of the tetramer has 6 alpha helixes
What is the result of increasing the extracellular K+ concentration?
This decreases the outward K+ gradient which makes the membrane potential less negative and helps to depolarize the cell
What is the result of increasing the intracellular K+ gradient?
This increases the outward K+ gradient which makes the membrane potential more negative and is hyperpolarizing
What is the membrane potential more positive than predicted by the Nernst equation, at low external K+ concentrations?
Because the membrane potential is also influenced by Na+ (which is accounted for by the Goldman- Hodgkin- Katz equation
What does depolarization mean?
Means more positive (less negative)
What does hyperpolarization mean?
Means more negative (less positive)
When does Na+ have the greatest influence on the membrane potential?
When the concentration of K+ is low. The lower the K+ concentration, the greater the influence of [Na+].
In the Goldman- Hodgkin- Katz equation, what is the alpha value?
Permeability of Na/ Permeability of K
Which ion has a greater permeability, K+ or Na+?
K+ (so K+ leaks out more reasily than Na+.
Can the alpha value change?
Yes, alpha can change when channels open because the permeability of ions change when channels open
Which theory accounts for the biological diversity of cell membrane diffusion potentials?
the Goldman- Hodgkin- Katz theory
What determines the cell resting potential for a given cell type?
The relative permeability of sodium to potassium. The greater the relative permeability, the more positive (or less negative) is the resting potential.
What is outward rectification?
The conductance of outward currents is greater than for inward currents
- Depolarization increases K+ conductance
- allows for repolarization
What is inward rectification?
the conductance of inward currents is greater than for outward currents
- Depolarization decreases K+ conductance
- maintains resting potential
In a Current Vs. Voltage graph, which way does an outward rectification slope?
Upward nonlinearly
In a Current Vs. Voltage graph, which way does an inward rectification slope?
Downward nonlinearly
What is the relationship between resistance and conductance?
Conductance is the inverse of resistance
Recification is a property of what?
a Channel
What is the process of electrodiffsion of K+ ions through their channel?
Single file, not passing one another. 3 K+ ions can be in the channel at once
What are the three states of volt-gated sodium and calcium channels?
1- Open
2- Closed (Inactivated)
3- Closed (Resting)
What state of volt-gated sodium and calcium channels is the basis of the refractory period?
Closed (inactivated)
What type of rectifiers are volt-gated sodium and calcium channels?
Outward rectifiers (because conductances are low at hyperpolarized voltages)
Following activation (volt-dependent opening of the m gate), what happens to the channels?
Channels rapidly and spontaneously progress to an inactivated state as the h-gates (inactivation gates) close
What is the difference between the absolute refractory period and the relative refractory period?
Absolutely no depolarization/ action potential can occur during the absolute.
In the relative, some of the channels have returned to the resting state so a larger stimulus can allow the cell to reach threshold and an action potential can be initiated
What period of cardiac action does the refractory period occur during?
Diastole. It allows for the heart to refill with blood and prevents the heart chambers from contracting before they have filled with blood
Can the degree of inactivation influence the size of a propagated action potential?
yes, if the initial resting potential is more depolarized than usual, some of the channels are still in the inactivated state, so the ensuing action potential is smaller and has a slower upstroke than normal
How are volt gated channels activated?
Charged transmembrane domains move when the voltage becomes more positive and this causes a conformational change of the channel pore that opens the channel.
Which type of channel is primarily responsible for the repolarization phase of the action potential?
The delayed outward rectifier K+ channels
When and how are the delayed outward rectifier K+ channels activated?
They activate upon depolarization, but with a time delay that allows a finite time for the depolarization phase of the action potential
How do delayed outward rectifier K+ channels inactivate?
Spontaneously via a ball and chain mechanism
Explain the ball and chain mechanism of delayed outward rectifier K+ channels.
a peptide domain that is attached to the beta subunit on the cytoplasmic side swings into an occluding position that results in inactivation
Which gate is the inactivation gate?
the h gate (intracellular gate)
Which gate is the activation gate?
the m gate (extracellular gate)
Where is the SA node located?
The base of the heart
Do cardiac action potentials look the same in all regions of the heart?
No, each region in the heart has a distinct action potential
What are the three factors influencing action potentials of the actrium, bundle of His, Purkinje network and ventrical cells?
1- Sodium dependent upstroke
2- Calcium dependent plateaus
3- Potassium-dependent repolarizations
What is the SA node upstroke dependent on?
Calcium channels
Which action potential is longer, skeletal muscle or cardiac muscle?
Cardiac muscle
Which cardiac action potential is the largest?
The purkinje fiber action potential
What favors the rapid propagation velocity in the His-Purkinje systen?
low internal resistance
What are the phases of purkinje fiber action potentials?
Phase O: Upstroke (fast inward sodium current that rapidly inactivated)
Phase 1: Transient repolarization (transient outward potassium currents)
Phase 2: Plateau (slow outward K currents and slow inward L-type calcium current that all slowly inactivate)
Phase 3: Repolarization (delayed outward rectifiers potassium currents, one is rapidly activated and one is slowly activated)
Phase 4: Resting potential (inward rectifier potassium currents
Which calcium channels are important in contributing to the generation of pacemaker currents in the SA node?
The T-type calcium channels
Why does the plateau phase occur?
-Resistance is low
-currents flow in both directions
K+ outward
Ca2+ inwards
Where are L-type Ca2+ channels located and what do they do at these locations?
Atria, ventricles and purkinje fibers –> Plateau
SA, AV –>Depolarization
Name some outward rectifying K+ currents and where they are located
- Ventricles and Purkinje - iKr and iKs
2. Atria - ikur
What is the Em for :
K+
Na+
ca2+
K+ = -90 mV
Na+ +60 mV
ca2+ = 120 mV
What is the resting potential of a neuron? of skeletal muscle?
Neuron = -70 mV
Skeletal Muscle = -85 mV
What is the resting potential of cardiac muscle:
- Atrial and Ventricular
- AV nodal cells
- SA nodal cells
- -80 mV
- -65 mV
- -55 mV
What is the resting potential of smooth muscle?
-55 mV
