Cardiac EC Coupling (B 2: W 2) Flashcards
What is the relationship between the ventricular action potential and the contraction?
There is one action potential for each contraction
There is a delay in eliciting a ctonraction
At which phase in the ventricular action potential is the peak contraction
Phase 3
What is the T tubule of a sarcomere and how does it function?
T tubule is an invagination of the plasma membrane into cell (skeletal and cardiac muscle)
Allows for rapid and homogenous spread of excitation to the center core of cell
- Electric signal travels across plasma membrane
- Contiguous membrane allows action potential to go inside cell
- Directly connected to the sarcoplasmic reticulum - reserve of calcium
- SR releases calcium to myofibrils to activate contraction - triggered by AP
How does cardiac muscle react to the removal of extracellular calcium? Skeletal muscle?
Cardiac muscle does not contract in the absence of extracellular calcium
Ca-dependent contraction
Skeletal muscle contractions increase in the absence of calcium
Why are T tubules in cardiac cells 5 times larger than in skeletal muscle?
Because cardiac cells require calcium to contract
Thinner T tubules would yield extracellular calcium depletion
How does extracellular calcium trigger increase in intracellular calcium to cause contraction?
- Extracellular calcium ions travel through voltage gated channels
-
Bind to RyR (ryanodine receptor)
- Release of Ca from sarcoplasmic reticulum
- Calcium induced calcium release
Does the addition of extracellular calcium affect contraction?
Yes - increases the force of contraction
What are the mechanisms for reducing calcium levels in a cell to cause relaxation?
- Reuptake of calcium by Ca-ATPase in sarcoplasmic reticulum
- Na-Ca exchange pump (NCX)
- No ATP
- Uses energy from Na gradient to pump Ca out
- 3 Na: 1 Ca
- Plasma membrane Ca pump: uses ATP
What are the roles of calcium current in cardiac excitation-contraction coupling?
- Responsible for maintaining the long plateau of the action potential
- Triggers the release of Ca ions from the sarcoplasmic reticulum
- Amplification of the plasma membrane signal
- Refills the sarcoplasmic reticulum Ca stores to be used in subsequent beats
How does the injection of a depolarizing current during a ventricular action potential affect contraction? Hyperpolarizing current?
AP shape is important for EC coupling
-
Depolarization of one AP increases force of contraction on the next beat
- Opened more Calcium channels, accummulated in SR, released on following beat
- Hyperpolarization of one AP decreases force of contraction in second beat
What happens in the case of premature systole?
- The premature systole is depressed - channels have not had time to recover from activation
- Second beat is stronger - extra calcium causes a transient increase
What happens when there is an increase in stimulation (increase in pacemaker activity)?
- Progressive increase of force over time
- More calcium is entering voltage-gated Ca channels
- More is being reuptaken into SR
How does the calcium, entering the cell and being released by SR, activate muscular contraction?
Binds to Troponin C
Which mechanism for calcium relaxation accounts for the highest decline in calcium concentration?
Reuptake by the SR Ca-ATPase
80% of rate of decline
Describe the mechanism for catecholamine activation of ß-adrenergic receptors in cardiac muscles.
- Epi/NE binds to ß receptor
- Coupled to a Gs protein
- Alpha G activates adenylyl cyclase
- Produces cAMP
- cAMP activates PKA
- PKA phosphorylates several targets
What are the two mechanisms of increasing contraction in the heart?
- PKA phosphorylates voltage-gated Ca channel
- Activity enhanced
- More Ca enters cell, causes more to be released from SR
- PKA phosphorylates PLB (phospholambin) to enhance Ca-ATPase reuptake activity into SR
- More Ca delivered in following beats
- Questionable third method: enhances coupling of Ca to RyR
What effect do catecholamines have on SA nodal cells?
Heart rate is increased
Same pathway as in ventricular cells - increases activity of Ifunny current
What are the two mechanisms of relaxation when catecholamines stimulate ß adrenergic receptors of the heart?
- PKA phosphorylates PLB (phospholambin)
- Increases activity of Ca-ATPase
- Faster reuptake of Ca into SR - relaxation
- PKA phosphorylates Troponin I
- Desensitizes troponin C to calcium
- Accelerates relaxation
How does tropomyosin inhibit actin-myosin interaction?
Tropomyosin lies on actin and prevents myosin from binding
When it moves, it allows actin and myosin to bind
Describe the troponin complex
Troponin T binds to tropomyosin
Troponin I and Troponin C bind to Troponin T
What is the structure of Troponin C?
“Dumbell”
4 potential binding sites for Ca and magnesium
I and II are Ca acceptor sites specifically
III and IV can bind Ca, but bing Mg if concentration is high
How does Troponin I function in the absence of calcium?
- Troponin I is not activated
- Pulls whole complex away from group - prevents interaction of actin with myosin
- In the presence of calcium, Ca binds Troponin C, and switches
- Actin-myosin interaction
Describe the molecular cycle of contraction
- ATP binds to polar heads of myosin
- Hydrolysis by myosin ATPase - now it is relaxed and energized
- Allows for binding of myosin head to actin filaments
- Once it binds, triggers change in angle of polar head
- Pulls the actin
- Motion and force being produced
- Now ATP needs to bind so molecule can come back to relaxed state
- ATP is necessary for unbinding and for hinge to be at normal angle
