52
CARDIOVASCULAR PHYSIOLOGY CONCEPTS
from the smooth muscle itself and is therefore
termed a myogenic response. This probably
results
from
stretch-induced
activation
of
ionic channels that leads to calcium influx.
Figure
3.9
illustrates
the
mechanism
by which an increase in intracellular cal-
cium
stimulates
vascular
smooth
muscle
contraction. An increase in free intracellu-
lar calcium can result from either increased
entry of calcium into the cell through L-type
calcium channels or release of calcium from
internal stores (e.g., sarcoplasmic reticulum).
The free calcium binds to a special calcium-
binding protein called calmodulin. The cal-
cium-calmodulin complex activates myosin
light chain kinase, an enzyme that phospho-
rylates myosin light chains in the presence of
ATP. Myosin light chains are regulatory subu-
nits found on the myosin heads. Myosin light
chain phosphorylation leads to cross-bridge
formation between the myosin heads and
the actin filaments, thus leading to smooth
muscle contraction.
Intracellular
calcium
concentrations,
therefore, are very important in regulating
smooth muscle contraction. The concentra-
tion of intracellular calcium depends on the
balance between the calcium that enters the
cells, the calcium that is released by intracel-
lular storage sites, and the movement of cal-
cium either back into intracellular storage
sites or out of the cell. Calcium is reseques-
tered by the sarcoplasmic reticulum by an
ATP-dependent calcium pump similar to the
SERCA pump found in cardiac myocytes. Cal-
cium is removed from the cell to the external
environment by either an ATP-dependent cal-
cium pump or the sodium-calcium exchanger,
as in cardiac muscle (see Chapter 2).
Several signal transduction mechanisms
modulate intracellular calcium concentration
and therefore the state of vascular tone. This
section describes three different pathways:
(1) IP3 via Gq-protein activation of phospho-
lipase C; (2) cAMP via Gs-protein activation
of adenylyl cyclase; and (3) cyclic guanosine
■ FIGURE 3.9 Regulation of vascular sm ooth muscle contraction by myosin light chain kinase (
MLCK
).
Increased intracellular calcium, by either increased entry into the cell (through L-type Ca++ channels) or
release from the sarcoplasmic reticulum
(SR),
forms a complex w ith calmodulin, activating MLCK, which
phosphorylates myosin light chains
(MLC),
causing contraction. Cyclic adenosine m onophosphate
(cAMP)
inhibits MLCK, thereby causing relaxation. Dephosphorylation of myosin light chains by MLC phosphatase
also produces relaxation.
ATP,
adenosine triphosphate; P, phosphate group.
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