Initiation Of Cardiac Action Potential Flashcards
What determines action potential propagation
- Difference in voltage between cells
- Resistance between cells
- Threshold for AP firing
- Size of the cells
- Expression level of voltage-gated Na channels (depolarization phase)
What initiates the cardiac action potential
Sino-atrial node (SAN) found in roof of right atria
What kind of channels does the sino-atrial node have?
Pacemaker channels called HCN channels (funny channels)
Describe pacemaker channels (HCN channel) structure and gating
-Structure similar to K+ channel
- non selective cation channel
- gated by cAMP
What does HCN channel stand for
Hyperpolarization-activated, cyclic nucleotide gated channel
State the pathway of electrical conduction in the heart
Sino-atrial node -> atrio-ventricular node -> bundle of his -> bundle branches -> purkinje fibers
How does the SA node action potential compare to the ventricular muscle action potential
- Slower upstroke velocity- b/c lack Na+ channels. Depolarization occurs by ICa
- Reduced plateau duration- caused by ICa inactivation after upstroke
- Diastolic depolarization- causes voltage dip below resting potential of SA node. This is due to pacemaker HCN channel. Note diastolic depolarization doesn’t occur in myocytes
- Higher resting potential- b/c lack IK1 which maintains the resting membrane potential
How many subunits does HCN channel have
4 subunits same as K+ channels
What is Ef value and what current is it for
Ef = -20 mV
Current is If= IHCN
What 2 channels are missing from SAN AP
Strong inward rectifier (Kir)
Na+ channel
When do HCN channels open
Turn on during repolarization, wind up hyperpolarizing membrane
What current causes the start of repolarization in SAN AP
Ik,DR
What current causes depolarization in SAN AP
ICa
How does sympathetic and parasympathetic stimulation effect diastolic depolarization slope
Sympathetic- increases diastolic depolarization slope, increase AP frequency
Parasympathetic- decreases diastolic depolarization slope, decreases AP frequency
What does the parasympathetic system control
Rest and digest
What does the sympathetic system control
Fight or flight. Stress, danger, physically active
Which HCN transmembrane segment (domain) binds cAMP
6
4 segments that span 1-6 transmembrane domains
How does the concentration of cAMP change with sympathetic stimulation?
CAMP concentration increases, due to more noradrenaline release (NA). This allows HCN channels to open sooner and pass a larger current (If).
How does the concentration of cAMP change with parasympathetic stimulation?
cAMP concentration decreases because acetylcholine (ACh) release acting on muscarinic 2 receptors causes a decrease in cAMP production (receptor inhibits adenylyl cylase (AC) reaction with ATP to produce cAMP)
What reaction produces cAMP
Adenylyl cyclase + atp = cAMP
How does sympathetic and parasympathetic stimulation shift the current vs voltage graph
Sympathetic- shift right
Parasympathetic- shift left
What does stimulation of the cardiac vagus nerve do
Causes heart rate to slow down.
We notice changes in Ca2+ entry and changes in cAMP
How does aerobic training affect vagal tone (vagus nerve) and in turn heart rate
Vagal tone increases, heart rate decreases
Features of the atrio-ventricular node
- Smaller cells
- Fewer gap junctions
- Slower intrinsic diastolic depolarization rate (slows conductance)
- More negative Em
