What is the primary role of cardiac myocytes?
Conraction
How is contraction initiated?
Action potential
What is action potential (AP)?
Transient change in polarization of resting membrane potential
Cardiac myocytes have an ___________________ b/w the intracellular and extracellular regions.
Electrical potential difference
The intracellular region of cardiac myocytes is _____________ charged relative to the extracellular region
Negatively
A resting ventricular myocyte has a resting membrane potential of ________ relative to the extracellular env.
-90 mV
What is the charge of the extracellular environment of a resting ventricular myocyte?
0 mV
T/F: The cardiac myocyte in a resting state is said to be depolarized, meaning there is charge separation b/w interior and exterior environments of the cell.
False
The Em is determined by _________________
[ion] differences
Which four ions are primarily involved in determining the membrane potential during the cardiac cycle?
- Na+
- K+
- Ca++
- Cl-
The current of cell membranes is carried by ______
ions
Which ion is most important for establishing the resting membrane potential?
K+
T/F: Ohm's Law states that the voltage difference b/w two points in a material are indirectly proportional to the current (I) and the resistance (R)
False
T/F: The inverse of current (I) is known as conductance (g).
False
V =
I*R
I = ΔV(1/R) =
ΔV*g
What factors are involved in the membrane potential?
- Type of cell
- [Ionic] differences
- Chemical gradient
- Electrochemical forces
- Permeability of cell membrane
- Electrogenic pumps
[K+] is _______ (high/low) on the inside of the cell.
High
Where will K+ want to move?
From inside to outside
Where will Na+ want to move?
From outside to inside
Where will Ca++ want to move?
From outside to inside
What equation can be used to calculate ion equilibrium?
Nernst
T/F: EK is not the same as Em because EK is less negative than Em
False
Why is there a small net electromotive driving force resulting in steady and slow leakage of K+ in resting nonpacemaker cardiomyocytes?
Negative voltage required to stop outward flow of K+ is not strong enough
What is responsible for the flow of K+ ions in the resting state?
Inward rectifier potassium channel (KI1)
The higher the permeability, the higher the ______________, meaning the greater the solute transport across the cell membrane
conductance
Where is the Na/K pump located?
Sarcolemma
If the ATPase Na/K pump is inhibited, what happens to intracellular Na?
Increases
Na/Ca exchanger rate (Na:Ca)
3:1
Na/K exchanger rate (Na:K)
3:2
A flux of positive charge into the resting cell results in a(n) __________ (inward/outward) current and ___(de-/hyper-)polarization of the cell.
Inward; depolarization
A flux of positive charge out of the resting cell results in a(n) __________ (inward/outward) current and ___(de-/hyper-)polarization of the cell.
Outward; hyperpolarization
T/F: Ion channels are glycosylated ptns w/ repeating domains
True
Each domain of ion channels consists of _____ transmembrane segments
6
Which ion channel has 4 domains that are not bonded together by peptide bonds?
K+
Which loop on the Na channel is believed to be the inactivation gate?
B/w domain III and IV
On the Na channel, where is the M gate located?
Outer side
On the Na channel, where is the H gate located?
Inner side
When a membrane is depolarized, which Na gate (H or M) rapidly opens allowing Na into the cell?
M
When does the H gate begin to close?
When the M gate starts to open, completely closes when cell starts to undergo repolarization
Sudden depolarization of membrane potential in cardiomyocytes via ion current results in __________
Action potential
List the 2 general types of cardiac APs
- Nonpacemaker ("fast response")
- Pacemaker ("slow response")
These cells are triggered by APs in adjacent cells w/ depolarizing currents
Nonpacemaker
These cells can spontaneously generate their own APs
Pacemaker
The nonpacemaker and pacemaker APs of the heart are different in their ______ and ______ than the APs found in nerve cells and skeletal muscle cells.
Shape; duration
Which cells have a true resting potential?
Nonpacemaker
Nonpacemaker AP is divided into how many phases?
5
Which phase of nonpacemaker cell:
Equilibrium maintained by high gK+ through inward rectifying K channel compared to low gNa+ and gCa++. This is true resting potential.
Phase 4
Which phase of nonpacemaker cell:
Rapid depolarization due to increase in Na conductance of voltage-gated fast ion Na channels. Rush of Na into cell.
Phase 0
Which phase of nonpacemaker cell:
Repolarization due to opening of transient outward K channel incombo w/ inactivation of Na channel. gCa++ increased and slow movement of Ca into cell via L-type Ca channel.
Phase 1
What channel is known as the slow inward, long-lasting current?
L-type Ca channel
Which phase of nonpacemaker cell:
Inward movement of Ca through lon-lasting (L-type) voltage gated Ca ion channel = major pathway of entry for Ca
Phase 2
Which phase of nonpacemaker cell:
Repolarization phase. gK conductance increases and initiates an outward K current through K delayed rectifier and gCa conductance decreases
Phase 3
Ventricular cells are unexcitable (refractory) during which phases (absolute refractory period)?
0, 1, 2
What does the effective refractory period include?
Absolute refractory period and some of phase 3
Which refractory period:
Weaker than normal APs may be generated and conducted.
Relative Refractory Period
Which refractory period:
Weaker than normal APs may be generated
Supranormal period
Which refractory period:
Only localized APs can be generated, but not propagated.
Effective Refractory Period
Which refractory period:
No new propagating APs are generated
Absolute refractory period
If the fast response Na channels are blocked/inactivated, the AP upstroke is reduced and can lead to ___________
Arrhythmias
During phase 3 or phase 4, nonpacemaker cells may start generating spontaneous depolarizations called _________________.
Afterpolarizations
T/F: The depolarizing current in an afterpolarization is from the fast response Na channel, given that the slow Ca channels are closed.
False
If a drug interacts w/ __________________ it can lead to dangerous arrhythmias
K delayed rectifier
T/F: Pacemaker cells have no true resting potential
True
What phases are the pacemaker AP divided up into?
0, 3, 4
Pacemaker cells are ______ and referred to as _________ AP compared to the "fast response" nonpacemaker cells.
Slow; slow response
What ion is responsible for being the major depolarizing current in pacemaker cells?
Ca (via long-lasting (L-type) voltage gated Ca channel)
Which phase of a pacemaker cell:
- gK decreases
- gCa is increasing (in second half of this phase) due to transient (T-type) Ca channels
- Pacemaker current (funny Na ion current)
- L-type Ca channels start to open
Phase 4
Which phase of a pacemaker cell:
- Inward movement of Ca via L-type Ca channels = depolarizes
- Simultaneous decrease in K channels currents
- Slope is "softer" than same phase of nonpacemaker cells
Phase 0
Which phase of a pacemaker cell:
Repolarization begins due to decrease in gCa and increase in gK
Phase 3
What is the primary pacemaker site?
SA node
What order of nodes would take over if the SA node failed?
SA node > AV node > Bundle of His > Purkinje fibers
The higher intrinsic "firing" rate of the SA node controls the other nodes. This is termed _____________
Overdrive suppression
If the SA node is no longer controlling, secondary pacemaker sites will develop. When this happens, the new site outside of the SA node is referred to as an ______________
Ectopic focus
What mechanisms can modify the SA node AP?
- Change slope of phase 4
- Alter the threshold voltage
- Change the hyperpolarization
What are the effects of sympathetic stimulation on the SA node?
Curve will shift to the left, meaning the AP will kick in faster
What are the effects of vagal (parasympathetic) stimulation on the SA node?
Curve will shift to the right, meaning the AP will take longer to kick in
List factors that would increase the SA node firing rate
- Sympathetic stimulation
- M antagonists
- Beta agonists
- Circulating catecholamines
- Hypokalemia
- Hyperthyroidism
- Hyperthermia
List factors that would decrease the SA node firing rate
- Parasympathetic stimulation
- M agonists
- Beta blockers
- Ischemia/hypoxia
- Hyperkalemia
- Na and Ca blockers
- Hypothermia