Week 1: cardiac excitability and excitation-contraction coupling Flashcards
Describe the cardiac conduction pathway.
- from SA node, impulses spread through right & left atrium via internodal pathways, and also to AV node
- AV node to Bundle of His
- bundle of his splits into left and right bundle branches on either side of inter ventricular septum–>Purkinjie fibers
- via Purkinjie fibers, action potential spread over endocardial surface (1st inter ventricular septum and papillary muscles, spreads down septum toward apex of heart) to epicardial surfaces
Describe the two types of action potentials in cardiac cells: fast response and slow response.
- Fast response: found in normal myocardial fibers in atria, ventricles, and Purkinjie fibers
- fast initial depolarization - Slow response: found in cells of SA and AV node
- slow initial depolarization
List the phases of the fast response action potential, including changes in ion conductances.
Phases:
- Rapid depolarization
- TTX (tetrodoxin) sensitive Na+ channels open ( in slow response, it is Ca2+ influx, no rapid Na channels in nodes) - Partial repolarization
- TTX sensitive Na+ channels close
- Ito (rapidly activating K+ channels) open
- inward rectifier K+ channels close - Plateau (Na+ and Ca2+ enter and K+ leave cell, are balanced)
- L-type Ca2+ channels open
- delayed rectifier K+ channels open
- Na/Ca exchange: Ca2+ inward
- Ito K+ channels close - Rapid repolarization
- L-type Ca2+ channels close
- more delayed rectifier K+ channels open
- Na/Ca exchange: Ca2+ outward - Phase 4
- delayed rectifier K+ channels close
- inward rectifier K+ channels open
Describe the two different voltage gated Ca2+ channels in cardiac cells and their functions: T type and L type
- T-type channels: in nodal cells
- not inhibited by dihydropyridines
- small transient current, activated by smaller depolarizations - L type channels: most common in cardiac muscle cells
- sensitive to dihydropyridine Ca blockers
- large and long lasting current, inactivate slowly, also found in T tubules of skeletal muscle
Describe what is occurring during the plateau (phase 2) phase of a fast response action potential.
Na+ and Ca2+ are entering the cell and K+ is leaving the cell.
- Ca2+ enter via L type calcium channels
- Ca also enters via Na/Ca exchange protein
What is QT syndrome?
A prolonged phase 2 (plateau). This can occur due to delayed opening of either inward rectifier or delayed rectifier channels for repolarization. Can also occur to to delayed closing of Na+ channel.
The sarcoplasmic reticulum of cardiac muscles doesn’t contain enough calcium. Describe the sources of Ca2+ for cardiac muscle contraction.
- release of Ca2+ from sarcoplasmic reticulum via ryanodine receptor (Ca channel). Triggered by influx of Ca through dihydrophyridine receptors (L type Ca channel)
- Ca entry from interstitial fluid through voltage gated Ca2+ channels
- Ca entry through Na/Ca exchange protein.
-this protein reverse directions: when greater than -20mV Ca goes in (means repolarization coupled with Ca efflux and muscle relaxation)
1,2,3 occurs during phase 2
Describe what happens to Ca2+ concentrations during cardiac muscle relaxation. Which phases does this occur?
70% of Ca transported back into SER by Ca-ATPase. Ca2+ also leaves by Ca/Na exchange protein (when membrane potential less than -20mV).
-Phase 3
Why does the SA node control the rate of heartbeat?
Overdrive suppression: SA node has fastest rate of spontaneous depolarization and therefore paces the heart, suppressing the pacemaking cells of the AV node and the Purkinjie fibers
Describe the ionic basis for cardiac automaticity.
If (or h): activated by hyperpolarization–> inward Na current –>depolarization (this inward Na+ current is what determines automaticity, slow depolarization of phase 4)
ICa: T-type Ca channels; inward Ca current –>depolarization
IK: delayed rectifier; outward K current; slowly activates during phase 2–>hyperpolarization and slowly inactivates during phase 4
How does the parasympathetic nervous system regulate heart rate?
Vagus nerve releases Ach
- binds to muscarinic AchR
- increases Iks potassium conductance (K+ out), which hyper polarizes the cell and reduces heart rate
How does the sympathetic nervous system regulate heart beat?
-release of norepinephrine
-increases cAMP phosphorylation of Ca channels (influx of Ca) and phosphorylation of phopholamban (increase rate of relaxation bc frees Ca-ATPase from inhibition by phospholamban, allowing faster uptake of Ca into SR)
-activation of delayed rectifier Iks current in phase 2 and 3 (shorten action potential)
-activation of If current (increase slope of phase 4 depolarization, more rapid onset)
Increased Ca influx causes increased excitability and increase force of contraction, faster rate of relaxation allows shorter action potential and capacity for higher frequency of firing
How do cardiac glycosides like digitalis work for treatment of congestive heart failure?
- inhibiting Na, K ATPase causes elevated Na+ in cell, partial depolarization (more +)
- this reduces Ca2+ efflux via Na/Ca exchange protein
- increases Ca2+ in cytoplasm, which is transported into SR, and becomes available for release upon stimulation
- more Ca2+ available to bind troponin and activate contractile proteins–>greater force of contraction
