Question

Proteins involved in smooth muscle contractions	Do you think progesterone will up- or down-regulate this protein?	How would this transcriptional regulation prevent uterine contractions?
Calcium channels
Calcium ATPase
Myosin light chain kinase
Myosin light chain phosphatase
Potassium channels
Oxytocin Receptors
Gap Junctions

Answer 1

In smooth muscle contraction calcium channel, Myosin light chain Kinase (MLCK), Myosin light chain phosphatase (MLCP), oxytocin receptors are also present in the smooth muscle. These proteins are involves in the smooth muscle contraction.

The calcium channel helps for entering the calcium ions from the extracellular fluid (ECF) to the sarcoplasm after excitation. This calcium ions induces more calcium ions release from the sarcoplasma reticulam. This calcium ion binds with calmodulin amd form calcium-calmodulin complex.

This complex activates the Myosin light chain Kinase (MLCK) protein for the phosphorylation of the myosin regulatory chain, after this phosphorylation, myosin head can bind with the actin filament to form cross bridge. This cross bridge formation of smooth muscle helps in the power stroke. For this power stroke the actin filament slides over myosin head and causes the smooth muscle contraction.

Myosin light chain phosphatase (MLCP) is a type of phosphatase enzyme that present inside the smooth muscle, which helps in the smooth muscle relaxation. After contraction phase this phosphatase enzyme causes dephosphorylation of the myosin regulatory chain. This dephosphorylation causes the stoppage of cross bridge formation and relaxes the contracted muscle.

The uterine smooth muscle and myoepithelial cells in the mammalary gland has oxytocin receptor. The oxytocin hormone binds with this receptor of thaose cells and activates IP3-DAG pathway. IP3 stimulates calcium release from the sarcoplasmic reticulum that causes smooth muscle contraction through calcium-calmodulin complex. DAG activates protein kinase C and MAP kinase pathway for prostaglandin production and ultimately causes smooth muscle contraction of those cells.

• Calcium ATPase is not involved in the smooth muscle contraction. It involves in the skeletal muscle contraction for hydrolysis of ATP and actively transported back into the cisternae. This lowers the cytoplasmic calcium and causes relaxation of skeletal muscle.
• Gap junction is not present in the smooth muscle. It present in the cardiac muscle and work as ion channel. This helps in the cardiac muscle contraction.

K+ channel involve in the regulation of vascular smooth muscle contraction and relaxation. Upon openning and closing of potassium channel the vascular smooth muscle contraction is regulated.

Role of progesteron on smooth muscle: Progesteron decreases the smooth muscle contraction in uterine smooth muscle. Progesteron down regulate the Myosin light chain Kinase (MLCK), Calcium channel proteins to decreases the activity of the uterus by lowering the pacemaker potential and calcium induced calcium release from the sarcoplasmic reticulum. This causes the inhibition of smooth muscle contraction.

Regulation to prevent uterine contraction: This prevention of uterine contration by progesteron is carried by the stimulation of myosin light chain phosphatase (MLCP),that enhances the dephophorylation of myosin regulatory chain that causes prevention of muscle contraction. The progesteron also open the K+ channels that causes hyperpolarization of the muscle and decrease calcium release. Finally this hyperpolarization causes smooth muscle relaxation and decreases uterine contraction.