Physiology 5th Ed.

SMOOTH MUSCLE

Smooth muscle lacks striations, which distinguishes it from skeletal and cardiac muscle. The striations found in skeletal and cardiac muscle are created by the banding patterns of thick and thin filaments in the sarcomeres. In smooth muscle, there are no striations because the thick and thin filaments, while present, are not organized in sarcomeres.

Smooth muscle is found in the walls of hollow organs such as the gastrointestinal tract, the bladder, and the uterus, as well as in the vasculature, the ureters, the bronchioles, and the muscles of the eye. The functions of smooth muscle are twofold: to produce motility (e.g., to propel chyme along the gastrointestinal tract or to propel urine along the ureter) and to maintain tension (e.g., smooth muscle in the walls of blood vessels).

Types of Smooth Muscle

Smooth muscles are classified as multiunit or unitary, depending on whether the cells are electrically coupled. Unitary smooth muscle has gap junctions between cells, which allow for the fast spread of electrical activity throughout the organ, followed by a coordinated contraction. Multiunit smooth muscle has little or no coupling between cells. A third type, a combination of unitary and multiunit smooth muscle, is found in vascular smooth muscle.

Unitary Smooth Muscle

Unitary (single unit) smooth muscle is present in the gastrointestinal tract, bladder, uterus, and ureter. The smooth muscle in these organs contracts in a coordinated fashion because the cells are linked by gap junctions. Gap junctions are low-resistance pathways for current flow, which permit electrical coupling between cells. For example, action potentials occur simultaneously in the smooth muscle cells of the bladder so that contraction (and emptying) of the entire organ can occur at once.

Unitary smooth muscle is also characterized by spontaneous pacemaker activity, or slow waves. The frequency of slow waves sets a characteristic pattern of action potentials within an organ, which then determines the frequency of contractions.

Multiunit Smooth Muscle

Multiunit smooth muscle is present in the iris, in the ciliary muscles of the lens, and in the vas deferens. Each muscle fiber behaves as a separate motor unit (similar to skeletal muscle), and there is little or no coupling between cells. Multiunit smooth muscle cells are densely innervated by postganglionic fibers of the parasympathetic and sympathetic nervous systems, and it is these innervations that regulate function.

Excitation-Contraction Coupling in Smooth Muscle

The mechanism of excitation-contraction coupling in smooth muscle differs from that of skeletal muscle. Recall that in skeletal muscle binding of actin and myosin is permitted when Ca2+ binds troponin C. In smooth muscle, however, there is no troponin. Rather, the interaction of actin and myosin is controlled by the binding of Ca2+ to another protein, calmodulin. In turn, Ca2+-calmodulin regulates myosin-light-chain kinase, which regulates cross-bridge cycling.

Steps in Excitation-Contraction Coupling in Smooth Muscle

The steps involved in excitation-contraction coupling in smooth muscle are illustrated in Figure 1-29 and occur as follows:

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Figure 1–29 The sequence of molecular events in contraction of smooth muscle. ADP, Adenosine diphosphate; ATP, adenosine triphosphate; Myosin~P, phosphorylated myosin; Pi, inorganic phosphate. CaM, calmodulin; ATPase, adenosine triphosphatase; IP3, inositol 1,4,5 triphosphate; SR, sarcoplasmic reticulum.

1.     Depolarization of smooth muscle opens voltage-gated Ca2+ channels in the sarcolemmal membrane. With these Ca2+ channels open, Ca2+ flows into the cell down its electrochemical gradient. This influx of Ca2+ from the ECF causes an increase in intracellular Ca2+ concentration. In contrast to skeletal muscle, where action potentials are required to produce contraction, in smooth muscle, subthreshold depolarization (which does not lead to an action potential) can open these voltage-gated Ca2+ channels and cause an increase in intracellular Ca2+ concentration. If the depolarization of the smooth muscle membrane reaches threshold, then action potentials can occur, causing even greater depolarization and even greater opening of voltage-gated Ca2+ channels.

Ca2+ that enters the smooth muscle cells through voltage-gated Ca2+ channels releases additional Ca2+ from the SR (called Ca2+-induced Ca2+ release). Thus, the rise in intracellular Ca2+ is partly due to Ca2+entry across the sarcolemmal membrane and partly due to Ca2+ release from intracellular SR stores.

2.     Two additional mechanisms may contribute to the increase in intracellular Ca2+ concentration: ligand-gated Ca2+ channels and inositol 1,4,5-triphosphate (IP3)–gated Ca2+ release channels. Ligand-gated Ca2+ channels in the sarcolemmal membrane may be opened by various hormones and neurotransmitters, permitting the entry of additional Ca2+ from the ECF. IP3-gated Ca2+ release channels in the membrane of the sarcoplasmic reticulum may be opened by hormones and neurotransmitters. Either of these mechanisms may augment the rise in intracellular Ca2+ concentration caused by depolarization.

3.     The rise in intracellular Ca2+ concentration causes Ca2+ to bind to calmodulin. Like troponin C in skeletal muscle, calmodulin binds four ions of Ca2+ in a cooperative fashion. The Ca2+-calmodulin complex binds to and activates myosin-light-chain kinase.

4.     When activated, myosin-light-chain kinase phosphorylates myosin light chain. When myosin light chain is phosphorylated, the conformation of the myosin head is altered, greatly increasing its ATPase activity. (In contrast, skeletal muscle myosin ATPase activity is always high.) The increase in myosin ATPase activity allows myosin to bind actin, thus initiating cross-bridge cycling and production of tension. The amount of tension is proportional to the intracellular Ca2+ concentration.

5.     Ca2+-calmodulin, in addition to the effects on myosin described earlier, also has effects on two thin filament proteins, calponin and caldesmon. At low levels of intracellular Ca2+, calponin and caldesmon bind actin, inhibiting myosin ATPase and preventing the interaction of actin and myosin. When the intracellular Ca2+ increases, the Ca2+-calmodulin complex leads to phosphorylation of calponin and caldesmon, releasing their inhibition of myosin ATPase and facilitating the formation of cross-bridges between actin and myosin.

6.     Relaxation of smooth muscle occurs when the intracellular Ca2+ concentration falls below the level needed to form Ca2+-calmodulin complexes. A fall in intracellular Ca2+ concentration can occur by a variety of mechanisms including hyperpolarization (which closes voltage-gated Ca2+ channels); direct inhibition of Ca2+ channels by ligands such as cyclic AMP and cyclic GMP; inhibition of IP3 production and decreased release of Ca2+ from sarcoplasmic reticulum; and increased Ca2+ ATPase activity in sarcoplasmic reticulum. Additionally, relaxation of smooth muscle can involve activation of myosin-light-chain phosphatase, which dephosphorylates myosin light chain, leading to inhibition of myosin ATPase.

Mechanisms That Increase Intracellular Ca2+ Concentration in Smooth Muscle

Depolarization of smooth muscle opens sarcolemmal voltage-gated Ca2+ channels and Ca2+ enters the cell from ECF. As already noted, this is only one source of Ca2+ for contraction. Ca2+ also can enter the cell through ligand-gated channels in the sarcolemmal membrane, or it can be released from the sarcoplasmic reticulum by second messenger (IP3)-gated mechanisms (Fig. 1-30). (In contrast, recall that in skeletal muscle the rise in intracellular Ca2+concentration is caused exclusively by release from the sarcoplasmic reticulum—Ca2+ does not enter the cell from the ECF.) The three mechanisms involved in Ca2+ entry in smooth muscle are described as follows:

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Figure 1–30 Mechanisms for increasing intracellular [Ca2+] in smooth muscle. ATP, Adenosine triphosphate; G, GTP-binding protein (G protein); IP3, inositol 1,4,5-triphosphate; PIP2, phosphatidylinositol 4,5-diphosphate; PLC, phospholipase C; R, receptor for hormone or neurotransmitter.

image Voltage-gated Ca2+ channels are sarcolemmal Ca2+ channels that open when the cell membrane potential depolarizes. Thus, action potentials in the smooth muscle cell membrane cause voltage-gated Ca2+channels to open, allowing Ca2+ to flow into the cell down its electrochemical potential gradient.

image Ligand-gated Ca2+ channels also are present in the sarcolemmal membrane. They are not regulated by changes in membrane potential, but by receptor-mediated events. Various hormones and neurotransmitters interact with specific receptors in the sarcolemmal membrane, which are coupled via a GTP-binding protein (G protein) to the Ca2+ channels. When the channel is open, Ca2+ flows into the cell down its electrochemical gradient. (See Chapters 2 and 9 for further discussion of G proteins.)

image IP3-gated Ca2+ channels are present in the sarcoplasmic reticulum membrane. The process begins at the cell membrane, but the source of the Ca2+ is the sarcoplasmic reticulum rather than the ECF. Hormones or neurotransmitters interact with specific receptors on the sarcolemmal membrane (e.g., norepinephrine with α1 receptors). These receptors are coupled, via a G protein, to phospholipase C (PLC). Phospholipase C catalyzes the hydrolysis of phosphatidylinositol 4,5-diphosphate (PIP2) to IP3 and diacylglycerol (DAG). IP3 then diffuses to the sarcoplasmic reticulum, where it opens Ca2+ release channels (similar to the mechanism of the ryanodine receptor in skeletal muscle). When these Ca2+ channels are open, Ca2+ flows from its storage site in the sarcoplasmic reticulum into the ICF. (See Chapter 9 for discussion of IP3-mediated hormone action.)

Ca2+-Independent Changes in Smooth Muscle Contraction

In addition to the contractile mechanisms in smooth muscle that depend on changes in intracellular Ca2+ concentration, the degree of contraction also can be regulated by Ca2+-independent mechanisms. For example, in the presence of a constant level of intracellular Ca2+, if there is activation of myosin-light-chain kinase, more cross-bridges will cycle and more tension will be produced (Ca2+-sensitization); conversely, if there is activation of myosin-light-chain phosphatase, fewer cross-bridges will cycle and less tension will be produced (Ca2+-desensitization).