General Principles of Gastrointestinal Function—Motility, Nervous Control, and Blood Circulation

Gastrointestinal Smooth Muscle Functions as a Syncytium.

The individual smooth muscle fibers in the gastrointestinal tract are 200 to 500 micrometers in length and 2 to 10 micrometers in diameter, and they are arranged in bundles of as many as 1000 parallel fibers. In the longitudinal muscle layer, the bundles extend longitudinally down the intestinal tract; in the circular muscle layer, they extend around the gut.

Within each bundle, the muscle fibers are electrically connected with one another through large numbers of gap junctions that allow low-resistance movement of ions from one muscle cell to the next. Therefore, electrical signals that initiate muscle contractions can travel readily from one fiber to the next within each bundle but more rapidly along the length of the bundle than sideways.

Each bundle of smooth muscle fibers is partly separated from the next by loose connective tissue, but the muscle bundles fuse with one another at many points, so in reality each muscle layer represents a branching latticework of smooth muscle bundles. Therefore, each muscle layer functions as a syncytium; that is, when an action potential is elicited anywhere within the muscle mass, it generally travels in all directions in the muscle. The distance that it travels depends on the excitability of the muscle; sometimes it stops after only a few millimeters, and at other times it travels many centimeters or even the entire length and breadth of the intestinal tract.

Also, because a few connections exist between the longitudinal and circular muscle layers, excitation of one of these layers often excites the other as well.

Slow Waves.

Most gastrointestinal contractions occur rhythmically, and this rhythm is determined mainly by the frequency of so-called “slow waves” of smooth muscle membrane potential. These waves, shown in Figure 63-3, are not action potentials. Instead, they are slow, undulating changes in the resting membrane potential. Their intensity usually varies between 5 and 15 millivolts, and their frequency ranges in different parts of the human gastrointestinal tract from 3 to 12 per minute—about 3 in the body of the stomach, as much as 12 in the duodenum, and about 8 or 9 in the terminal ileum. Therefore, the rhythm of contraction of the body of the stomach, the duodenum, and the ileum is usually about 3 per minute, about 12 per minute, and 8 to 9 per minute, respectively.

The precise cause of the slow waves is not completely understood, although they appear to be caused by complex interactions among the smooth muscle cells and specialized cells, called the interstitial cells of Cajal, which are believed to act as electrical pacemakers for smooth muscle cells. These interstitial cells form a network with each other and are interposed between the smooth muscle layers, with synaptic-like contacts to smooth muscle cells. The interstitial cells of Cajal undergo cyclic changes in membrane potential due to unique ion channels that periodically open and produce inward (pacemaker) currents that may generate slow wave activity.

The slow waves usually do not by themselves cause muscle contraction in most parts of the gastrointestinal tract, except perhaps in the stomach. Instead, they mainly excite the appearance of intermittent spike potentials, and the spike potentials in turn actually excite the muscle contraction.

Spike Potentials.

The spike potentials are true action potentials. They occur automatically when the resting membrane potential of the gastrointestinal smooth muscle becomes more positive than about −40 millivolts (the normal resting membrane potential in the smooth muscle fibers of the gut is between −50 and −60 millivolts). Note in Figure 63-3 that each time the peaks of the slow waves temporarily become more positive than −40 millivolts, spike potentials appear on these peaks. The higher the slow wave potential rises, the greater the frequency of the spike potentials, usually ranging between 1 and 10 spikes per second. The spike potentials last 10 to 40 times as long in gastrointestinal muscle as the action potentials in large nerve fibers, with each gastrointestinal spike lasting as long as 10 to 20 milliseconds.

Another important difference between the action potentials of the gastrointestinal smooth muscle and those of nerve fibers is the manner in which they are generated. In nerve fibers, the action potentials are caused almost entirely by rapid entry of sodium ions through sodium channels to the interior of the fibers. In gastrointestinal smooth muscle fibers, the channels responsible for the action potentials are somewhat different; they allow especially large numbers of calcium ions to enter along with smaller numbers of sodium ions and therefore are called calcium-sodium channels. These channels are much slower to open and close than are the rapid sodium channels of large nerve fibers. The slowness of opening and closing of the calcium-sodium channels accounts for the long duration of the action potentials. Also, the movement of large amounts of calcium ions to the interior of the muscle fiber during the action potential plays a special role in causing the intestinal muscle fibers to contract, as we discuss shortly.

Changes in Voltage of the Resting Membrane Potential.

In addition to the slow waves and spike potentials, the baseline voltage level of the smooth muscle resting membrane potential can also change. Under normal conditions, the resting membrane potential averages about −56 millivolts, but multiple factors can change this level. When the potential becomes less negative, which is called depolarization of the membrane, the muscle fibers become more excitable. When the potential becomes more negative, which is called hyperpolarization, the fibers become less excitable.

Factors that depolarize the membrane—that is, make it more excitable—are (1) stretching of the muscle, (2) stimulation by acetylcholine released from the endings of parasympathetic nerves, and (3) stimulation by several specific gastrointestinal hormones.

Important factors that make the membrane potential more negative—that is, that hyperpolarize the membrane and make the muscle fibers less excitable—are (1) the effect of norepinephrine or epinephrine on the fiber membrane and (2) stimulation of the sympathetic nerves that secrete mainly norepinephrine at their endings.

Entry of Calcium Ions Causes Smooth Muscle Con­traction.

Smooth muscle contraction occurs in response to entry of calcium ions into the muscle fiber. As explained in Chapter 8, calcium ions, acting through a calmodulin control mechanism, activate the myosin filaments in the fiber, causing attractive forces to develop between the myosin filaments and the actin filaments, thereby causing the muscle to contract.

The slow waves do not cause calcium ions to enter the smooth muscle fiber (they only cause entry of sodium ions). Therefore, the slow waves by themselves usually do not cause muscle contraction. Instead, it is during the spike potentials, generated at the peaks of the slow waves, that significant quantities of calcium ions enter the fibers and cause most of the contraction.

Tonic Contraction of Some Gastrointestinal Smooth Muscle.

Some smooth muscle of the gastrointestinal tract exhibits tonic contraction as well as, or instead of, rhythmical contractions. Tonic contraction is continuous; it is not associated with the basic electrical rhythm of the slow waves but often lasts several minutes or even hours. The tonic contraction often increases or decreases in intensity but continues.

Tonic contraction is sometimes caused by continuous repetitive spike potentials—the greater the frequency, the greater the degree of contraction. At other times, tonic contraction is caused by hormones or other factors that bring about continuous partial depolarization of the smooth muscle membrane without causing action potentials. A third cause of tonic contraction is continuous entry of calcium ions into the interior of the cell brought about in ways not associated with changes in membrane potential. The details of these mechanisms are still unclear.

The parasympathetic supply to the gut is divided into cranial and sacral divisions, which were discussed in Chapter 61.

Except for a few parasympathetic fibers to the mouth and pharyngeal regions of the alimentary tract, the cranial parasympathetic nerve fibers are almost entirely in the vagus nerves. These fibers provide extensive innervation to the esophagus, stomach, and pancreas and somewhat less to the intestines down through the first half of the large intestine.

The sacral parasympathetics originate in the second, third, and fourth sacral segments of the spinal cord and pass through the pelvic nerves to the distal half of the large intestine and all the way to the anus. The sigmoidal, rectal, and anal regions are considerably better supplied with parasympathetic fibers than are the other intestinal areas. These fibers function especially to execute the defecation reflexes, discussed in Chapter 64.

The postganglionic neurons of the gastrointestinal parasympathetic system are located mainly in the myenteric and submucosal plexuses. Stimulation of these parasympathetic nerves causes general increase in activity of the entire enteric nervous system, which in turn enhances activity of most gastrointestinal functions.

Afferent Sensory Nerve Fibers From the Gut

Many afferent sensory nerve fibers innervate the gut. Some of the nerve fibers have their cell bodies in the enteric nervous system and some have them in the dorsal root ganglia of the spinal cord. These sensory nerves can be stimulated by (1) irritation of the gut mucosa, (2) excessive distention of the gut, or (3) the presence of specific chemical substances in the gut. Signals transmitted through the fibers can then cause excitation or, under other conditions, inhibition of intestinal movements or intestinal secretion.

In addition, other sensory signals from the gut go all the way to multiple areas of the spinal cord and even to the brain stem. For example, 80 percent of the nerve fibers in the vagus nerves are afferent rather than efferent. These afferent fibers transmit sensory signals from the gastrointestinal tract into the brain medulla which, in turn, initiates vagal reflex signals that return to the gastrointestinal tract to control many of its functions.

Gastrointestinal Reflexes

The anatomical arrangement of the enteric nervous system and its connections with the sympathetic and parasympathetic systems support three types of gastro­intestinal reflexes that are essential to gastrointestinal control: