CARDIAC UNIT: IONIC BASIS OF THE CARDIAC ACTION POTENTIAL Flashcards
Define: ion channel
protein that sits in the membrane and lets ions flow through it.
Describe the structure of potassium channels (K+)
- Voltage gated channel
- 4 α subunits and 1 𝛽 subunit
- 6 transmembrane segments per α subunit
Describe the structure of sodium channels (Na+)
- Voltage gated channel
- Consists of 𝛽1, 𝛽2, and α subunits .
- 𝛽 subunits modify membrane expression and behaviour of α subunits
- α subunit has 4 domains
- 1 domain = 6 transmembrane segments
- Total of 24 transmembrane segments per α subunit
Describe the structure of calcium channels (Ca2+)
- 2 α subunits
- α1 has 4 domains
- α2 - δ (alpha delta) subunit; joined by an S-S bond
- 1 ß subunit
Define: Ohms Law
Give the equation
Ohm’s Law: states that the current through a conductor between two points is directly proportional to the voltage across the two points
I = delta V x G
Where:
- V1: membrane potential (Emor Vm)
- V2: equilibrium potential for that ion (example: equilibrium potential for K+ is EK)
- G: conductance - the ability to conduct current
What two forces that act on an ion when it moves
- Electrical gradient
- Concentration gradient
Define: Nernst Equation
Give the equation
Nernst equation: describes the concentration gradient into electrical terms.
EK = (RT/zF) ln ([K+]out/[K+]in)
Where:
R: gas constant
T: temperature
z: valence
F: Faraday’s constant
ln: natural log
Give the equilibrium potential for:
- potassium
- sodium
- calcium
EK = -90 mV
ENa = +65 mV
ECa
At rest: +120 mV
During contraction: +90 mV
Describe the Goldman-Hodgkin-Katz Equation
Goldman-Hodgkin-Katz Equation: Describes the influence of the different ions on the membrane voltage
NOTE: the membrane potential is closest to the Eqm potential of the ion that permeates the membrane most freely
- If K+ permeates, then Em is close to EK
- If Na+ permeates, then Em moves closer to ENa
What does the conductance of an ion depend on
- whether ion channels are open
- number of channels present
At resting membrane potential, what ion has the highest conductance?
K+
- ions that cross the membrane are K+ ions
- membrane potential is close to Ek (which is -90mV)
membrane potential: ~80 mV
During depolarization, what channels open?
Sodium (Na+) channels open
- ions crossing the membrane are Na+ ions
- membrane potential moves toward ENa (which is +65mV)
membrane potential gets to +30mV
opening threshold is -55mV
Compare action potentials between motor neurons, skeletal muscle, and cardiac ventricle
- cardiomyocyte action potential is relatively long
- In skeletal muscle, twitch comes after action potential; happens in series
- In cardiac myocyte, the time where twitch and action potential overlap slightly
- cardiomyocyte action potential has a plateau phase while the others do not
Compare tension regulation between skeletal muscle and cardiac muscle
In skeletal muscle, there is variable recruitment of muscle fibres. In cardiac muscle, there is 100% recruitment of muscle fibres with every beat.
In skeletal muscle, the first action potential causes a twitch and the second and subsequent action potentials build upon the first. This is called summation and can lead to tetanus.
In cardiac muscle, there is no tetany possible due to the long action potential duration
Describe phase 4 of the cardiomyocyte action potential
- This is the resting membrane potential.
- Kir2.1 (inward rectifying) potassium channels are open allowing K+ to move into the cell.
- The resting membrane potential is -90 millivolts
Describe phase 0 of the cardiomyocyte action potential
- The membrane depolarizes and voltage gated sodium channels (Nav1.5) open.
- They open at ~-55mV
What is the affect of tetrodotoxin on voltage gated sodium channels?
Inhibits voltage gated sodium channels?
Describe phase 1 of the cardiomyocyte action potential
rapid repolarization of the membrane potentials occurs in this phase
- a transient outward current of K+ is caused by the opening of Kv4.3 channels (Ikto)
Describe phase 2 of the cardiomyocyte action potential
- Unique to cardiac muscle.
- Prolongs the action potential. Plateau has a variable duration.
- Note, polyamines are blocking IK1 in this phase, meaning IK1 are not causing depolarization anymore
The main currents of this phase are
- Ica: Voltage gated calcium channels open (Cav1.2) and Ca+ in)
- INCX (sodium calcium exchanger): antiporter membrane protein that allows 3 sodiums into cell and 1 Ca2+ out of the cell; This is a net depolarizing current
Explain how calcium affects the cardiomyocyte action potential duration
Reduced flow of Ca2+ ions reduces the action potential duration and thus force production.
This shortens the plateau phase of the cardiomyocyte action potential.
State the dominant ion at different phases of the cardiomyocyte action potential
phase 4: potassium
phase 0: sodium
phase 2: calcium
phase 3: potassium
Define: rectification
Rectification: conductance of ions through a channel is greater in one direction than the other
When active, is IKDR an outward or inward rectifier? When is IKDR active?
outward rectifier when active. their purpose is to help repolarize the cell
Active and open with depolarization. Inactive at negative currents because their job is done!
When active, is IK1 an outward or inward rectifier? When is IK1active?
inward rectifier. Moves K+ ions into cell.
However, when the membrane depolarizes there is a small amount of outward current of K+ allowed before IK1 is blocked by polyamines
What 3 currents make up the IKDR (potassium delayed rectifier current)
- slow delayed rectifier Iks (Kv7.1)
- rapid delayed rectifier Ikr (Kv11.1)
- Ultra-rapid delayed rectifier Ikur (Kv1.5)
define: inward rectifier
Inward rectifier: passes inward current more easily than outward; physiologically, outward current is more important
define: delayed rectifier
Delayed rectifier: only passes outward current. “Delayed” because slower than INa; includes IKs, IKr, IKur
define: absolute refractory period
Absolutely refractory period: where another action potential cannot be generated as sodium channels are still in inactive position and haven’t recovered
- covers phase 0-2
define: relative refractory period
Relative refractory period: many sodium channels have activated already and another action potential can be elicited but at a greater cost
- occurs in last half of phase 3 and a little bit therafter
