CHAPTER 5Excitable Tissue: Muscle 111C, which produces IP 3 and allows for Ca2+ release through
IP 3 receptors. In the intact animal, stimulation of cholinergic
nerves causes release of acetylcholine, excitatory potentials,
and increased intestinal contractions.
Like unitary smooth muscle, multiunit smooth muscle is
very sensitive to circulating chemical substances and is nor-
mally activated by chemical mediators (acetylcholine and
norepinephrine) released at the endings of its motor nerves.
Norepinephrine in particular tends to persist in the muscle
and to cause repeated firing of the muscle after a single stimu-
lus rather than a single action potential. Therefore, the con-
tractile response produced is usually an irregular tetanus
rather than a single twitch. When a single twitch response is
obtained, it resembles the twitch contraction of skeletal mus-
cle except that its duration is 10 times as long.RELAXATION
In addition to cellular mechanisms that increase contraction
of smooth muscle, there are cellular mechanisms that lead to
its relaxation (Clinical Box 5–3). This is especially important
in smooth muscle that surrounds the blood vessels to increase
blood flow. It was long known that endothelial cells that line
the inside of blood cells could release a substance that relaxed
smooth muscle (endothelial derived relaxation factor,FIGURE 5–20 Sequence of events in contraction and
relaxation of smooth muscle. Flow chart illustrates many of the mo-
lecular changes that occur from the initiation of contraction to its re-
laxation. Note the distinct differences from skeletal and cardiac muscle
excitation.
FIGURE 5–21 Effects of various agents on the membrane
potential of intestinal smooth muscle. Drugs and hormones can al-
ter firing of smooth muscle action potentials by raising (top trace) or
lowering (bottom trace) resting membrane potential.
Binding of acetylcholine to
muscarinic receptorsActivation of calmodulin-dependent
myosin light chain kinaseIncreased myosin ATPase activity
and binding of myosin to actinContractionPhosphorylation of myosinIncreased influx of Ca^2 + into the cellDephosphorylation of myosin by
myosin light chain phosphataseRelaxation, or sustained contraction
due to the latch bridge and
other mechanismsAcetylcholine, parasympathetic
stimulation, cold, stretchMembrane potentialEpinephrine, sympathetic
stimulationmV0− 50CLINICAL BOX 5–3
Common Drugs That Act on Smooth Muscle
Overexcitation of smooth muscle in the airways, such as
that observed during an asthma attack, can lead to bron-
choconstriction. Inhalers that deliver drugs to the conduct-
ing airway are commonly used to offset this smooth muscle
bronchoconstriction, as well as other symptoms in the
asthmatic airways. The rapid effects of drugs in inhalers are
related to smooth muscle relaxation. Rapid response in-
haler drugs (eg, ventolin, albuterol, sambuterol) frequently
target β-adrenergic receptors in the airway smooth muscle
to elicit a relaxation. Although these β-adrenergic receptor
agonists targeting the smooth muscle do not treat all
symptoms associated with bronchial constriction (eg, in-
flammation and increased mucus), they are quick and fre-
quently allow for sufficient opening of the conducting air-
way to restore airflow, and thus allow for other treatments
to reduce airway obstruction.
Smooth muscle is also a target for drugs developed to in-
crease blood flow. As discussed in the text, NO is a natural
signaling molecule that relaxes smooth muscle by raising
cGMP. This signaling pathway is naturally down-regulated
by the action of phosphodiesterase (PDE), which trans-
forms cGMP into a nonsignaling form, GMP. The drugs
sildenafil, tadalafil, and vardenafil are all specific inhibitors
of PDE V, an isoform found mainly in the smooth muscle in
the corpus cavernosum of the penis (see Chapter 25). Thus,
oral administration of these drugs can block the action of
PDE V, increasing blood flow in a very limited region in the
body and offsetting erectile dysfunction.