Smooth muscle contraction is regulated by calcium levels within the cell. An increase in calcium occurs through ligand-gated calcium channels or release from intracellular stores, activating myosin light chain kinase which phosphorylates myosin for contraction. Relaxation is driven by reducing calcium through reuptake into stores and removal from the cell by transporters, activating myosin light chain phosphatase to dephosphorylate myosin and cause relaxation. Nitric oxide also stimulates relaxation through cGMP-dependent phosphorylation.

1. Smooth muscle

2. Smooth muscle
• Smooth muscles have molecular structures similar to those in striated
muscle, but the sarcomeres are not aligned so as to generate the striated
appearance.
• Smooth muscles contain α-actinin and tropomyosin molecules, as do
skeletal muscles.
• They do not have the troponin system, and the light chains of smooth
muscle myosin molecules differ from those of striated muscle myosin.
• Regulation of smooth muscle contraction is myosin-based, unlike striated
muscle, which is actin based.
• However, like striated muscle, smooth muscle contraction is regulated by
Ca2+.

5. Smooth muscle contraction
• Smooth muscle contraction is
dependent on calcium influx.
• Calcium is increased within the
smooth muscle cell through two
different processes.
• First, depolarization, hormones, or
neurotransmitters cause calcium
to enter the cell through L-type
channels located in the membrane.
• Intracellular calcium then stimulates
the release of calcium from the
sarcoplasmic reticulum (SR) by way
of ryanodine receptors and IP3; this
process is referred to as calcium-
induced calcium release

6. • Once calcium has entered the
cell it is free to bind
calmodulin, which transforms
into activated calmodulin.
• Calmodulin then activates the
enzyme myosin light chain
kinase (MLCK), MLCK then
phosphorylates a regulatory
light chain on myosin.
• Once phosphorylation has
occurred, a conformational
change takes place in the
myosin head; this increases
myosin ATPase activity which
promotes interaction
between the myosin head and
actin.

7. • ATPase activity is much lower in
smooth muscle than it is in skeletal
muscle.
• This factor leads to the much slower
cycling speed of smooth muscle.
• Smooth muscle contraction is
enhanced even further through the
use of connexins. Connexins allow for
intercellular communication by
allowing calcium and other
molecules to flow to neighboring
smooth muscle cells. VGCC-voltage gated Ca2+ channel

8. Smooth muscle relaxation
• Relaxation of smooth muscle. Smooth
muscle relaxation occurs either as a result of
removal of the contractile stimulus or by the
direct action of a substance that stimulates
inhibition of the contractile mechanism.
• Regardless, the process of relaxation
requires a decreased intracellular
Ca2+ concentration and increased MLC
phosphatase (myosin light chain
phosphatase) activity.
• The sarcoplasmic reticulum and the plasma
membrane contain Ca,Mg-ATPases that
remove Ca2+ from the cytosol.
• Na+/Ca2+ exchangers are also located on the
plasma membrane and aid in decreasing
intracellular Ca2+. During relaxation,
receptor- and voltage-operated
Ca2+ channels in the plasma membrane
close resulting in a reduced Ca2+ entry into
the cell.

9. Nitric oxide role in smooth muscle
contraction
• Another important clinical aspect of smooth
muscle relaxation is the mechanism of nitric
oxide.
• Nitric oxide is formed via nitric oxide synthase in
endothelial cells; it is then able to diffuse out of
the endothelium into smooth muscle cells.
• Nitric oxide then induces the conversion of
guanosine triphosphate (GTP) to cyclic
guanosine monophosphate (cGMP) by binding to
and activating the enzyme guanylyl cyclase.
• In smooth muscle cells, the increase in cGMP
will lead to stimulation of cGMP-dependent
protein kinase which in turn activates MLCP
(myosin light chain phosphatase), leading to
dephosphorylation of myosin light chains and
eventual smooth muscle relaxation.

10. Contraction
• Rise in intracellular calcium ions (Ca2+)
• action potential depolarizes plasma
membrane
• L-type voltage-gated Ca2+ channels open,
causing intracellular Ca2+ levels to rise
• Ca2+ are sequestered in sarcoplasmic
reticulum inside the cell
• when excited, Ca2+ channels on sarcoplasmic
reticulum membrane open
• free Ca2+ are released into the cytoplasm
• Ca2+ bind to calmodulin, which induces
conformational change
• Ca2+-calmodulin (CaM) complex activates
the myosin light-chain kinase (MLCK)
• this phosphorylates myosin light chain (MLC)
and triggers actin-myosin binding and
smooth muscle contraction
Relaxation
• Nitric oxide
• nitric oxide is a soluble guanylyl
cyclase that produces cyclic
guanosine monophosphate
(cGMP)
• cGMP activates protein kinase G,
which activates MLCP
• Myosin light chain phosphatase
(MLCP)
• dephosphorylates and inactivates
MLC allowing the myofibrils to
relax