Smooth Muscle

Smooth muscle is sometimes called involun­tary muscle because it is found in structures that are not voluntarily or consciously regu­lated (e.g., gastrointestinal tract, blood vessels, reproductive tract).

About 1% of the smooth muscle of the animal body is multiunit smooth muscle (e.g., iris and ciliary body of the eye and pilomotor fibers that erect the hair in the skin). in this type of smooth muscle, the contraction of each individual smooth muscle cell is more depen­dent on its autonomic innervation. Gap junc­tions are not prevalent between these cells.

Structure

The smooth muscle cell is a fusiform (spindle­shaped) contractile unit with a central nucleus. size of smooth muscle fibers varies consider­ably. Most cells are 50-250 μm long and 5­10 μm in greatest diameter. The major portion of the cell consists of sarcoplasm. No cross­striations, myofibrils, or sarcolemma are easily visible with the light microscope (see Fig. 1-6). Filaments are present as actin and myosin mol­ecules, but there are no orderly arrangements to form striations. interactions between actin and myosin filaments (i.e., sliding filaments) are believed to be the basis for smooth muscle contractions, but the characteristic shortening of sarcomeres is not seen because there is no distinct organization of the filaments.

Like skeletal muscle, smooth muscle cells can hypertrophy to increase the size of organs. However, unlike skeletal muscle, smooth muscle cells can also divide mitotically to increase the number of cells. For example, the increase in size of the uterine wall during preg­nancy to several times its nonpregnant volume is due in considerable measure to an increase in the amount of smooth muscle in the wall. some of the increase is due to an increase in size of individual muscle fibers, but there is also an increase in the number of cells. This hyper­trophy and hyperplasia in the uterus are under the influence of reproductive hormones. Late in pregnancy there is also a change in the structure of the cell membranes of uterine smooth muscle cells. An increase in gap junctions between cells in late pregnancy sets the stage for the mechani­cal and electrical coupling between smooth muscle cells that will be necessary for normal parturition. in general, the structure and func­tion of smooth muscle are more subject to modification by external factors, such as hor­mones, than are those of skeletal muscle.

Stress-Relaxation

smooth muscle exhibits a special property called stress-relaxation, or plasticity. This is the ability to adjust to stretching without increasing the final tension or the pressure exerted on the contents within a hollow viscus surrounded by smooth muscle. As the muscle stretches, the tension increases at first, but then in a few seconds or a few minutes the smooth muscle relaxes again to its original tension, even though it is still elongated.

This stress-relaxation occurs in the stomach when it is filling with food, in the intestines as the processed food moves along, in the blood vessels when the blood volume increases, in the urinary bladder as it increases its volume of urine, and in the uterus as pregnancy develops.

Plasticity allows expansion of stretch within physiologic limits without an increase in pres­sure and without pain; the smooth muscle does not lose its contractile ability. The reverse occurs upon emptying of a visceral organ when the stretched muscle shortens back to its origi­nal length: all tension is lost at first but returns shortly. Plasticity is believed to be due to changes in the arrangement or binding of the myosin and actin filaments upon stretching or shortening.

Contraction and Relaxation

All skeletal muscle contraction depends on Ach release at a neuromuscular junction and the generation and propagation of action poten­tials on the cell membrane. This is not the case for smooth muscle. The stimuli that bring about smooth muscle contraction and relaxation are quite variable. Thus, smooth muscle is a much more functionally diverse tissue than skeletal muscle.

The contraction and relaxation of most smooth muscle are much slower events than the rapid muscle twitch that is characteristic of skeletal muscle. This permits the maintenance of a relatively constant pressure with the use of little cell energy. This is characteristic of smooth muscle in organs that require a constant state of tone or some degree of contraction for normal function (e.g., smooth muscle in the walls of blood vessels).

Role and Sources of Calcium

As in skeletal muscle, contraction and relax­ation of smooth muscle are linked to the Ca²⁺ concentration in the cytosol of smooth muscle cells. However, how this concentration is regu­lated and the role of Ca²⁺ in the contraction process is quite different in the two types of muscle. some calcium is stored in the sarco­plasmic reticulum of smooth muscle cells, but many types of smooth muscle cells also contain a significant number of calcium channels in the outer cell membrane (Fig. 8-8). These calcium channels may be either voltage-gated or ligand­gated, and the smooth muscle within a given organ may have both types of channels or pri­marily only one type of channel.

An understanding of the role of calcium channels in the outer cell membrane of smooth muscle cells led to the develop­ment of a group of drugs termed calcium channel blockers. These agents are capable of binding to and inactivating these calcium channels, and this tends to reduce the strength of contractions. Smooth muscle cells in the walls of many arterial blood vessels have these types of channels, and this type of drug has been proved effective in lowering blood pressure in both humans and animals.

When cytosolic Ca²⁺ increases within smooth muscles, calcium ions bind to a regulatory protein (calmodulin) (Fig.8-8). Unlike skeletal muscle, whose regulatory proteins are associ­ated with the actin filaments, the calmodulin in smooth muscle is associated with the heads of myosin molecules in myosin filaments. The binding of calcium to calmodulin activates a kinase, also associated with myosin, and this kinase phosphorylates other sites on myosin. This phosphorylation ultimately results in con­traction, so myosin phosphorylation is a key regulatory step (Fig. 8-8). This is in contrast to skeletal muscle, whose myosin does not require phosphorylation. For relaxation, the phosphor­ylation of myosin is reversed by other intracel­lular enzymes that are always present and active (Fig. 8-8). This reversal and relaxation can occur when the cytosolic calcium concentra­tion is reduced.

Figure 8-8. Sources and role of calcium ions in the initiation and regulation of smooth muscle con­traction. Dotted lines associated with calcium ions indicate move­ment by diffusion. solid lines associated with calcium ions indicate removal of calcium from the cytosol to promote relaxation. Relaxation can also be promoted by the action of other intracellular enzymes that dephosphorylate myosin.

Unlike skeletal muscle, some smooth muscle responds to certain stimuli by relaxation or a reduction in contraction strength. For example, stimulation of β₂-adrenergic receptors on airway smooth muscle in the lungs produces relax­ation and an increase in airway diameter. in general, this type of relaxation is due to either a reduction in the number or availability of calcium channels in the cell membrane or a reduction in the phosphorylation of myosin within the myofilaments of smooth muscle cells.

Action Potentials and Slow Waves

Not all smooth muscle cells have action poten­tials on their cell membranes during contrac­tion and relaxation. cells with predominantly ligand-gated calcium channels in their cell membranes may undergo a contraction-relax­ation cycle without action potentials. The cell membrane may depolarize slightly because of the entry of calcium, but no action potential is seen. smooth muscle cells that do have action potentials during contraction have both sodium and calcium electrically gated channels in their cell membrane.

Action potentials in skeletal muscle occur after the binding of Ach to its cell membrane receptors. in smooth muscle, action potentials can be elicited by a variety of stimuli.

The visceral or single-unit smooth muscle in some organs (the gastrointestinal tract being the classic example) exhibit a unique type of membrane electrical activity termed slow waves. These are waves, or periods, of spontaneous fluctuations in the resting membrane potential that spread throughout a body of smooth muscle and typically occur at some regular rhythm (Fig. 8-9). Slow waves alone do not cause contractions, but action potentials may occur at the peak of these waves, and the action potentials are associated with contractions (Fig. 8-9). Because action potentials and contrac­tions are seen only at the peak of the slow waves, the rate at which slow waves develop determines the rate at which smooth muscle contractions can occur. The precise origin of the slow waves is uncertain, but a variety of stimuli, such as hormones, neurotransmitters, and the local chemical environment, can deter­mine whether action potentials occur at the peak of the slow waves. The relationship between slow-wave activity and action poten­tials is important in the regulation of gastroin­testinal motility and is discussed in more detail in Chapter 21.

Action potentials spread across groups of single-unit smooth muscle fibers because of gap junctions between the fibers (where the plasma membranes of adjacent cells touch). Thus, single-unit smooth muscle cells can be linked electrically while remaining indepen­dent chemically (no secretion of transmitter substance from cell to cell is required).

Figure 8-9. Slow-wave electrical activity in smooth muscle with action potentials occurring at the peak of slow waves.

Autonomic Innervation

In visceral or single-unit smooth muscle, the fibers of the autonomic nervous system travel between the smooth muscle cells in a branch­ing network of terminal fibrils. These fibrils have varicosities (beadlike enlargements) at intervals along their axons. When action poten­tials depolarize them, the transmitter substance is released and diffuses to the smooth muscle cell membranes of several cells, where stimula­tion occurs. in multiunit smooth muscle, a branch of an autonomic nerve innervates each muscle fiber. This provides more direct neural control of each muscle cell, but the junction between neuron and muscle is less highly structured than the neuromuscular junction of skeletal muscle. For both types of smooth muscle, the innervation is usually dual; that is, both divisions of the autonomic nervous system innervate smooth muscle. important excep­tions are blood vessels (arteries, arterioles, and veins), which have predominantly sympathetic innervation, and in the skin, where the pilomo­tor fibers and sweat glands receive only sympa­thetic innervation.

Acetylcholine is released from the parasym­pathetic postganglionic nerve fibers and norepi­nephrine from the sympathetic postganglionic fibers. The response of smooth muscle (contrac­tion or relaxation) to these neuromediators depends on the type of autonomic receptor (see Tables 10-1 and 10-2) on the smooth muscle and the intracellular events initiated by the binding of the neuromediators to their recep­tors. For example, stimulation of β₂-adrenergic receptors causes smooth muscle relaxation, while stimulation of α₁-adrenergic receptors causes smooth muscle contraction. some smooth muscle can also be stimulated to con­tract by stimulation of muscarinic receptors by ACh. individual smooth muscle cells may have multiple types of receptors in their cell mem­branes and respond to both autonomic neu­rotransmitters. in this case, the overall response of the smooth muscle also depends on the rela­tive levels of the different neurotransmitters.