Cardiac Exam Lecture #5 (E-C Coupling) Flashcards
Explain how sympathetic stimulation affects the Cardiac Excitation Coupling on a Grand Scheme (Think of the giant diagram)
This is the adrenergic signaling cascade: catecholamines bind to beta adrenergic receptors, which stimulates adenylyl cyclae, which increases cAMP, which activates PKA. PKA does various things, It phosphorylates the L type calcium channel (more CICR), it phosphorlyates the RyR (conducts more calcium), it phosphorylates phospholamben, which then causes SERCA activity to increae; it also phosphorlyates troponin I which lowers calcium affinity/sensitivity, which you want so that calcium can unbind quickly and you can get quicker relaxation. 80% if the calcium in the cell is circulated through the SERCA pump loop. The other 20% is released outside of the cell by calcium ATPases, or the sodium calcium exchanger.
What do cardiac glycosides do?
Cardiac glycosides inhibit the Na/K pump, which results in intracellular Na+ accumulation, less calcium leaves the cell which causes stronger and faster contraction
Cardiac glycosides are POSITIVE INOTROPIC agents
Explain the function of the following structures:
Sarcolemma
Transverse/”T” tubules
Sarcoplasmic reticulum (terminal cisternae and longitudinal cisternae)
Troponin C
Sarcolemma: propogation of AP’s, controls calcium influx into the cell via activation of slow inward calcium current
T tubules: transmit electrical activity to cell interior, located at the Z lines
Sarcoplasmic Reticulum: intracellular calcium storage site
- terminal cisternae: lots of RyR in this region, CICR site to initiate contraction
- longitudinal cisternae: site of calcium reuptake to initiate relaxation
Troponin C: Ca2+ receptor on contractile (actin) protein
Explain the “Mechanism of EC Coupling in Cardiac Muscle” aka explain CICR
- AP conducts along surface membrane and down into T tubules
- Depolarization of T tubules activates Ca2+ influx via slow inward calcium currnet (voltage sensor in L type channel)
- Influx of calcium binds to RyR and activates calcium release from the SR
- Calcium released from the SR binds to troponin C to initiate cell contraction
- Process known as CICR
- Contraction is maintained as long as cytosolic calcium remains elevated
- Relaxation is initiated when cytosolic calcium is removed by
- SR calcium reuptake (80%)
- Calcium efflux via Na/Ca exchange (18%)
- Calcium efflux via sarcolemnal Ca pump (2%)
Compare and contrast cardiac and skeletal muscle based on cell size, how they are activated, what is their contraction dependent on, what is the contraction amplitude regulated by, do they have summation, aerobic vs anaerobic
Explain contraction.
What is the common misconception about contraction?
Explain isometric contraction vs isotonic contraction
Contraction: process by which muscle generates tension or force
Note: muscle contraction is not always associated with muscle shortening
Isometric Contraction: contraction WITHOUT shortening (no change in length) If a muscle is unable to generate enough force to meet the afterload, the contraction is isometric
Isotonic: contraction with shortening and constant force
During normal cardiac cycle, cardiac muscle intially generates isometric tension and then isotonic contractions
What are the four factors that determine cardiac output?
Which have a positive effect vs which have a negative effect?
Four Factors that Determine Cardiac Output:
- Heart Rate (positive effect)
- Preload (positive effect)
- Myocardial Contractility (positive effect)
- Afterload (negative effect)
Define preload, afterload, and contractility
Preload: load on the muscle BEFORE contraction is initiated, preload is dependent on ventricular filling (end-diastolic volume)
Afterload: the load on the muscle AFTER contraction is initiated, afterload is any force that resists muscle shortening, normally arterial pressure is the force that resists left ventricle contraction
Contractility: the inherent ability of actin and myosin to form crossbridges and generate contractile force. Contractility is INDEPENDENT of preload and afterload, it’s primarily determined by intracellular Calcium concentration
Draw the graph that explains the length-tension relationship when it comes to preload
What happens to strength of contraction when you stretch the heart?
What happens cellularly when you stretch cardiac muscle?
An increase in resting cardiac muscle length will increase contractile strength (direct relationship)
Stretching cardiac muscle:
- creates more optimal overlap between thick and thin filaments
- increases calcium sensitivity of myofilaments
- enhances intracellular SR calcium release (possibly through release of Nitric Oxide)
Describe the effects of changing preload on isotonic contractions
An increase in preload increases the amount of isotonic muscle shortening (note that maximum tension remains constant)
Therefore, an increase in preload increases the stroke volume/cardiac output
A decrease in preload decreases the amount of muscle shortening
Explain the effects of changing afterload on isotonic contraction
What happens to stroke volume as you increase afterload?
Increase in afterload will DECREASE stroke volume because you are decreasing the amount of isotonic muscle shortening
Draw a tension as a function of time graph in regards to contractility. Describe what affect increased and decreased contractility has.
At constant afterload and preload what does an increase in contractilty do?
What does a decrease in contractility do?
At constant preload and afterload, increase in contractility increases the amount of shortening by allowing the muscle to reach a shorter length.
A decrease in contractility decreases the amount of muscle shortening by not allowing the muscle to reach a shorter length.
Draw the graph of shortening velocity as a function of force/afterload.
When pressure the heart is fighting against is high… velocity of shortening is…?
What is maximal isometric force?
Increasing afterload/force decreases the velocity of isotonic muscle shortening. Vmax represents the maximal velocity of shortening with “no load”
When the pressure the heart is fighting against is high velocity of shortening is low.
Maximal isometric force: is when the muscle is unable to meet the afterload, aka at zero velocty of shortening
Explain how the force-velocity relationship is altered by changes in preload
Explain how the force velocity graph is affected by changing contractility
Draw the “positive and negative staircase” as well as another depiction explaining PVCs and PESP
Explain what is going on
Positive staircase: as HR increases the strength of contraction increases. Mechanism: more calcium influx per unit time
Negative Staircase: decrease in heart rate results in decrease of contraction strength. Mechanism: less calcium influx per unit time
PVC/premature beat: smaller than normal contraction because there is less time for calcium to become available for contraction
PESP/”post extrasystolic potentiation”: stronger than normal contraction of beat following a premature beat because there is more time for calcium to become available for contraction
