M2 L4 Flashcards
What is excitation-contraction coupling
ACh release starts excitation-contraction coupling by making the muscle fiber fire an action potential. This signal spreads and causes the release of Ca²⁺, which leads to muscle contraction.
- excitation is the action potential at NMJ
- elevation of Ca2+ starts off contraction
Discuss the steps for excitation at the neuromuscular junction
- Motor neuron depolarizes and the contents are released into the synaptic cleft (orange)
- the released Act diffuses to the pre-synaptic membrane. It must pass through the basement membrane first.
- Ach molecules bind to Ach Receptors (ligand gated - Ach is the ligand). (pink)
- Ach receptors opens due to a conformational change which lets in Na+. (pink)
- The voltage gated Na+ channels speed things up and propegate action potential. the channel is located all along surface. (neon blue)
- After Ach binds to receptor, AchE hydrolyzes (breaks down) Ach which is essential for ending the signal between the neuron and the muscle
- Once ACh is broken down by AChE, it is released from the ACh receptor (AChR)
- After ACh is released, the ACh receptors (AChR) return to their closed conformation.
How does Ca2+ get delivered to the myofibrils deep within the membrane of a muscle?
The t-tubules allow the depolarization to reach deeper into the muscle.
is depolarization of the NMJ alone is not enough to cause muscle contraction.
No, the depolarization of the NMJ alone is not enough to cause muscle contraction. It initiates an action potential that travels through the T-tubules to the sarcoplasmic reticulum, which releases calcium ions. These calcium ions then allow the myosin heads to bind to actin and perform the power stroke, resulting in muscle contraction. So, excitation-contraction coupling is required for contraction.
Experiments showed that extracellular Ca2+ was not needed for contraction, so where is the Ca2+ coming from?
The sarcoplasmic reticulum provides Ca2+. Once the t-tubule depolarized it causes release of Ca from SR via FEET PROCESSES
what are feet processes
structures connecting t-tubules and SR to get release of Ca2+
What is needed for Ca2+ to reach the sarcomere?
mechanically coupled transmembrane proteins (from both t-tubule and SR)
Discuss transmembrane protein of T-tubule
* type of channel
* other name
- voltage gated Ca2+ channels - voltage from depolarization comes in from the t tubule and then the VG Ca2+ channels open and opens the RyR
- DHP channels
- the VG configuration changes when the membrane depolarizes
Discuss transmembrane protein of SR
* type of channel
* other name
- Ca2+ release channel
- Ryanodine receptors (RyR)
How does depolarization of the T-tubule membrane cause the SR to release Ca2+?
Depolarization of the T-tubule membrane activates dihydropyridine receptors (DHPRs), which are voltage-sensitive. DHPRs then trigger ryanodine receptors (RyR) on the sarcoplasmic reticulum (SR), causing the SR to release Ca²⁺ into the muscle cytoplasm, initiating contraction.
How do we get Ca2+ back into the SR?
By the SERCA pump (Sarcoplasmic/Endoplasmic Reticulum Ca²⁺-ATPase). This active transport pump uses ATP to move Ca²⁺ against its concentration gradient, restoring low cytosolic calcium levels and allowing muscle relaxation.
What is the molecular switch needed to allow the modulation of Ca2+ to generate force?
The molecular switch is the troponin-tropomyosin complex. When Ca²⁺ binds to troponin, it causes tropomyosin to shift, exposing myosin-binding sites on actin. This allows cross-bridge formation and force generation. When Ca²⁺ is removed, tropomyosin blocks the binding sites, stopping contraction.
What three things is the troponin complex made of? What do they each do?
3 Troponin proteins:
* TN T: binds to tropomyosin and moves it to the right area
* TN I: lies on top of MHC binding site blocks during low Ca2+)
* TN C: binds Ca2+
How does the troponin complex look with low Ca2+
The troponin complex covers the myosin binding sites.
TN I is currently blocking the binding site and preventing cross bridge formation
How does the troponin complex look with high Ca2+
The troponin complex moves away because Ca2+ binds to TN C which causes a conformational change that exposes the myosin binding site.
What is the molecular switch needed to allow the modulation of Ca2+ to generate force for the areas that aren’t covered by the troponin complex?
The areas not covered by the troponin complex are regulated by tropomyosin. Tropomyosin runs along the actin filament, blocking myosin-binding sites in a resting state. When Ca²⁺ binds to troponin, it causes tropomyosin to shift, exposing the 7 myosin binding sites for myosin, allowing contraction to occur.
What is a twitch and when does it occur?
a partial activation of cross-bridge cycling, generating a small, brief contraction called a muscle twitch.
If not enough Ca²⁺ is available to bind all troponin molecules, only some myosin-binding sites on actin are exposed.
What mechanisms do we have to modulate Ca2+ release levels?
- Summation: increase frequency of stimulation
- modify how fast muscle contraction stimulation is
- increase firing of motor neurons (drives higher Ca2+ until u maintain it)
twitch ,summation, and tetanus differences + graph
- Twitch – single, brief muscle contraction caused by one action potential. Ca²⁺ is released but quickly pumped back, so force is small and short-lived.
- Summation – When multiple action potentials arrive before the muscle fully relaxes, more Ca²⁺ stays in the cytoplasm, leading to stronger contractions as twitches add up.
- Tetanus – A sustained, maximal contraction due to high-frequency stimulation, where Ca²⁺ remains elevated, keeping actin-binding sites exposed for continuous cross-bridge cycling.
What happens with an increased amount of Ca2+
There will be more cross bridges formed because calcium will have a better chance of being bound to troponin
What would happen if the myosin head stiffened and was only able to bend to 60 degrees
instead of the normal 90 degrees?
The power stroke is weaker and there’s a lower range of motion and the velocity decreases.
The pivoting movement (power stroke) is smaller.
Less actin sliding occurs, meaning less sarcomere shortening and weaker contractions. The force generated per stroke is lower, making muscle contractions less effective.
Explain the difference between the conformation of the Troponin complex and tropomyosin at
low and high calcium levels.
Low Ca²⁺: Troponin is in its resting conformation, keeping tropomyosin in a position that blocks myosin-binding sites on actin, preventing contraction.
High Ca²⁺: Ca²⁺ binds to troponin, causing a conformational change that shifts tropomyosin, exposing myosin-binding sites, allowing cross-bridge formation and contraction.
