M2 L8 Flashcards
Way to regulate cytosol calcium levels: ligand gated Ca2+ channel
* where found
* receptor ex:
- surface membrane
- P2X receptor - ATP is the ligand that binds to it
Way to regulate cytosol calcium levels: VG Ca2+ Channels
- where found
- receptor ex:
- phasic or tonic?
- found on surface membrane
- DHP R
- could be phasic or tonic
Way to regulate cytosol calcium levels: SR Ca2+ release
* how released
- released with RyR (When some Ca²⁺ enters the cell, it triggers RyR on the SR to release even more Ca²⁺)
- IP3R - secondary messenger (IP₃ binds to IP₃R on the SR, causing Ca²⁺ release.)
Way to regulate cytosol calcium levels: Ca2+ pump/SERCA
* where located
* what do
- membrane surface
- pumps ca2+ back into extracellular space and back into SR
What 4 things can pump Ca2+ into the cytosol
1) DHP R
2) P2XR
3) IP3R
4) RyR
What can pump Ca out of Cytosol?
SERCA
Once a NT diffuses, continue the process
it diffuses until it binds to alpha adrenergic receptor and then binds via G protein and activates phospholipase Cx
Activating MLC:
When you elevate Ca2+ through any mechanism - what does it bind to?
After Ca2+ binds to BLANK, what gets activated?
What happens once this thing is activated?
binds to calmodulin which then activates MLC kinase
it activates myosin light chain kinase (MLCK) - need this step for contraction to occur
Once MLCK is activated, it phosphorylates the myosin light chain (MLC), allowing myosin to interact with actin and generate force for contraction.
What do you do if you need to remove Ca2+?
You need a phosphotase
Ca²⁺ is actively removed by SERCA (into SR), PMCA (out of cell), or NCX (exchanges Ca²⁺ for Na⁺).
With low Ca²⁺, calmodulin (CaM) is inactive, so MLCK stops phosphorylating MLC.
Myosin light chain phosphatase (MLCP) removes the phosphate from MLC, fully stopping cross-bridge cycling and relaxing the muscle.
Main diff in cross bridge cycling between smooth and skeletal muscle
smooth muscle:
* calmodulin
* modulated by MLC (doesn’t do anything in skeletal)
- In smooth muscle, there’s no troponin, so contraction depends on MLC phosphorylation:
skeletal muscle:
* contains troponin complex
- In skeletal muscle, contraction is controlled by Ca²⁺ binding to troponin, which moves tropomyosin and allows myosin to bind actin.
MLC phosphorylation steps?
In smooth muscle, there’s no troponin, so contraction depends on MLC phosphorylation:
1) Ca²⁺ binds to calmodulin (CaM)
2) Calmodulin activates MLCK
3) MLCK phosphorylates MLC, allowing MHC to bind actin → contraction
4) When Ca²⁺ is removed, MLCP dephosphorylates MLC, stopping contraction
Discuss differences between initiation of skeletal vs smooth muscle
Skeletal: release of NTs from NMJ
Smooth: no NMJs gets activated by NTs & soluble factors
Discuss differences between propagation of skeletal vs smooth muscle
Skeletal: all or none contraction initiated by action potential
Smooth: all or none contraction initiated by action potential OR graded responses
Discuss differences between source of Ca2+ for skeletal vs smooth muscle
Skeletal: intracellular (SR)
Smooth: intracellular (SR) and extracellular
Discuss differences between regulation of Ca2+ for skeletal vs smooth muscle
Skeletal: DHPR-RyR coupling
Smooth: VG Ca2+ channels, ligand-gated, RyR, secondary messenger
Discuss differences between regulation of cross bridges for skeletal vs smooth muscle
Skeletal: depends on troponin complex
Smooth: depends on MLC phosphorylation and kinase activation
