PHYL3001 Lecture Notes - Lecture 9: Guanine, Diglyceride, Protein Kinase C
LECTURE NINE: Calcium Sensitization
Calmodulin Response to Ca2+:
• Calmodulin (CalM) binds Ca2+
• Ca-CalM binds to and activated myosin light chain kinase (MLCK)
• MLCK phosphorylates myosin on serine 19 of the regulatory light chain
(RLC or MLC20)
Myosin Phosphorylation:
• Myosin
o 2 heavy chains → where heads are located
o 2 light chains → one is RLC
• Un-phosphorylated myosin has low affinity to actin
• Little ATP activity → no power stroke
• Myosin light chain phosphatase keeps muscle relaxed → keeps myosin
un-phophorylated
• Most myosin is un-phosphorylated
• Phosphorylation rate increased when MLCK is activated through Cal-CalM
and contraction is produced
Force and Calcium:
• Intracellular calcium measured in smooth muscle loaded with calcium
sensitive dyes
• High intracellular calcium levels not maintained during agonist
stimulation
• Agonist stimulation (e.g. ACh) produces more force at the same
intracellular calcium concentration than depolarization
• Agonist stimulation produced large changes in force and phosphorylation
with little change in intracellular calcium
Calcium Sensitization:
• Contractile agents can increase the sensitivity of the contractile system to
calcium
• Inhibitory agonist can reduce the sensitivity of the contractile system to
calcium
• Change happens between calcium and phosphorylation of myosin →
predicts force
• Sensitization is mostly due to changes in the amount of myosin
phosphorylation
• Force vs. myosin phosphorylation is same for K+ (open circles) and ACh
(closed circles) contractions
Mediation of Calcium Sensitization:
• Inhibition of the small monomeric G-protein Rho prevents calcium
sensitization
• Rho is a monomeric G-protein → binds GTP
• Not related to the trimeric G-proteins that interact with GPCR like Gq, Gs
etc.
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