Download III. Smooth muscle cell structure

MCB 32 FALL 2000
CARDIAC MUSCLE AND HEART
SMOOTH MUSCLE AND BLOOD VESSELS
Reading: Chapter 6, especially pp 170-178
I.
Cellular electrical and mechanical activity in heart: Figs 6.21 and 6.22
Mechanism of electrical excitation: action potential. Every beat of the heart has
to be preceded by an electrical excitation. Different from skeletal muscle in that the
electrical excitation comes from the heart itself, and nerves (autonomic, involuntary)
regulate the rate of excitation. Another difference is that excitation of one cardiac cell
leads to conduction of the action potential to all the other cells in the heart because the
cells are coupled together by gap junctions, which insure electrical continuity between
cells. Cardiac cells are also mechanically attached by little spot welds (called
desmosomes or intercalated disks) between cells near the gap junctions. These
mechanical attachments help to assure that the gap junctions do not fall apart from each
other.
Mechanism of cardiac cell contraction: Ca entry into the cytosol due to release of
Ca from the SR (stored there due to activity of Ca pump that uses ATP to accumulate Ca
to high concentration, in mM range). Ca release from SR is somewhat different from that
in skeletal muscle in that SR release sites need to be triggered by Ca entering across the
plasma membrane due to opening of Ca channels during the action potential. This
“trigger Ca” acts on SR release sites to open them, releasing flood of Ca into the cytosol.
The Ca then operates similar to skeletal muscle:
Ca  Troponin  Tropomyosin  allow actin and myosin to bind and contract
Ca removal following action potential: Ca pump into SR and out across the plasma
membrane. Na/Ca exchange (also called an antiporter) in plasma membrane transports
Na into cell from outside (where [Na] is high) to inside the cell (where [Na] is low) and
Ca from the cytosol (where [Ca] is low) to outside (where [Ca] is high). This also
contributes to relaxation.
II.
Important aspects of cardiac action potential: gradual depolarization,
regulation, and extended duration
A. Refractory period of skeletal muscle vs cardiac muscle: Fig. 6.23
Periodic contraction and relaxation of cardiac muscle is crucial. It does no good
for heart muscle to maintain constant tension/contraction like skeletal muscle can do.
How is this periodicity assured?
Longer refractory period of cardiac muscle assures that relaxation will occur
before another action potential is generated. Longer refractory period is caused by the
longer action potential duration of cardiac muscle.
II.
Smooth muscle controls blood vessel contraction
Smooth muscle cells are wrapped around the outsides of blood vessels, which
conduct the blood from heart to all the tissues of the body. Constraction of this smooth
muscle leads to reduction in the diameter of the vessel, making it harder for blood to flow
through. This control permits blood vessels to divert blood to tissues that need extra
blood supply (e.g., exercising muscle). This contraction of the vessels is also a way for
the system as a whole to control blood pressure, which has to be maintained at a proper
level to support blood flow all around the circulatory system, including up to the head.
III.
Smooth muscle cell structure
As shown in Figs 6.24 and 6.25, smooth muscle cells are quite different from
skeletal muscles in that they are not nearly as regularly arranged as skeletal or cardiac
muscle. They have one nucleus only, and are therefore capable of dividing, unlike
skeletal and cardiac muscle.
Although smooth cells contract using actin and myosin, these proteins are not as
well organized as in the other two types of muscle. Actin and myosin “sarcomeres” are
arranged at oblique angles to the long axis of the muscle fiber. Actin is attached to the
cell membrane of smooth muscle cells at sites called “dense bodies” using specialized
proteins. These dense bodies also appear in the cytosol to permit attachments within the
cells, similar to the z-lines of skeletal muscle.
Cells are often attached to each other by desmosomes. Some types of smooth
muscle have gap junctions between cells which assure that electrical impulses in one cell
can be conducted to the next cell to provide coordinated contraction, e.g., smooth muscle
in the gastrointestinal tract, which has peristaltic waves that move from one end of the
intestine to the other.
IV.
Smooth muscle mechanical and electrical activity Figs 6.28 and 6.29
Smooth muscle also has quite different mechanical and electrical properties
compared to skeletal and cardiac (see Table 6.3):.
Mechanical contraction is controlled by the entry of Ca into the cells from both
outside the cell through Ca channels and also release from the sarcoplasmic reticulum,
which is only sparse compared to skeletal and heart muscle. In addition, smooth muscle
has two different mechanisms in the SR for releasing Ca: the ryanodine receptor (like
cardiac and skeletal muscle) and inositol trisphosphate (IP3) receptor (like in nonexcitable cells) are both present. The former release Ca during Ca entry from outside the
cell through Ca channels (so-called calcium-induced Ca release) while the latter release
Ca in response to hormone and nerve-induced increases in cell [IP3].
Many smooth muscles can contract in the absence of fully developed action
potentials. Ca channels in the plasma membrane can be opened without full
depolarization as occurs in cardiac and skeletal muscle. Any Ca that enters smooth
muscle cytosol from either outside or from the SR leads to increased contraction.
Like cardiac muscle but unlike skeletal muscle, both autonomic nerves
(sympathetic release norepinephrine, parasympathetic release acetylcholine) and
hormones (e.g., epinephrine) modulate the rates (and strength) of contraction. The
automonic nerves innervate the muscles, but the terminals are sort of “strung” along the
length of the muscles and are not so well defined as in skeletal muscle. The autonomic
nerves often induce action potentials, which are generated by voltage-regulated Ca (not
Na) channels. There can also be local regulation by factors released within tissues, e.g.,
histamine (paracrine action).
Smooth muscle (unlike skeletal muscle) contraction occurs over a very broad
range of lengths. This can be seen in Fig. 6.29. This is useful for tissues that must
contract under very different conditions, e.g., urinary bladder or stomach (or uterus!)
when they are filled compared to when they are quite empty.
Smooth muscle can contract for extended periods of time because it is quite
efficient compared to skeletal and cardiac muscle.
Smooth muscle contraction is controlled by Ca, but in a very different way from
the way skeletal and cardiac muscle are controlled. It is called myosin-based regulation.
A regulatory protein called myosin light chain sits on myosin head and becomes
phosphorylated by myosin light chain kinase, which transfers a terminal phosphate from
ATP to the MLC. This phosphorylation of MLC allows the actin and myosin to interact,
and they will continue to contract (just as in skeletal or cardiac muscle) as long as MLC
is phosphorylated. Activity of MLC kinase is in turn controlled by the amount of Ca in
the cytosol, with MLC kinase remaining active as long as [Ca] is elevated. During
relaxation, [Ca] in the cytosol decreases, MLC kinase is inactivated, and MLC becomes
dephosphorylated by MLC phosphatase.