Smooth muscle and Motility in the GI tract

Activation of smooth muscle contraction by Ca++

1 Cytosolic Ca++ increases 2a Ca++ binds to calmodulin in cytosol 2b Ca++-calmodulin complex binds to myosin light chain kinase 3 Activated myosin light chain kinase phosphorylates myosin cross-bridges 4 Phosphorylated cross-bridges bind to actin filaments 5 Cross-bridge cycle produces tension and shortening 6 Decreased Ca++ activates myosin light chain phosphatase to dephosphorylate myosin

Stool contents

Amount per day: 150 grams (~ 0.33 pounds) Contents: Water (2/3 of weight) Undigested polysaccharides of diet: cellulose Bacteria of colonic origin Fat from colonic bacteria Cholesterol Bile salts Ions: K+, Na+ , Cl-, Ca2+, Fe2+ Osmolality of normal stool: 290-300 mOs/kg

Activation of smooth muscle contraction by Ca++

Cross bridge cycling is similar to skeletal muscle. Cycles of ATP binding and hydrolysis by myosin generates movement of actin relative to myosin to generate forceful movement

Ileocecal sphincter is located between the small intestine and colon.

In addition to controlling the movement from the small gut to colon, it blocks colonic content entering the small gut.

Typical structure of the gut wall

Mucosa Submucosa Muscularis externa

Ileocecal valve

Normally closed to prevent colonic contents from moving back into ileum. Stimulated to relax (open) each time an ileal contraction approaches. Distension or chemical irritation of the large intestine produces a reflex contraction (closure).

Smooth muscle structure

Smooth muscles are spindle shaped, have a single nucleus, and do not have striations. Most smooth muscles in the gut are electrically coupled by gap junctions, forming a functional syncytium.

Phasic Contraction

contract and relax rapidly, occurs periodically, serve to mix and advance chyme through the organs esophagus, gastric antrum, small intestine, colon

Vomiting Reflex can be triggered by

distension of stomach distension of the small intestine toxic substances acting upon chemoreceptors in intestinal wall or brain pressure in the skull rotating movements of the head (motion sickness) intense pain tactile stimulus of back of throat (gag reflex)

Upper esophageal sphincter (UES)

is normally contracted and when food stimulates the swallowing center in the medulla, UES relaxes allowing passage of food into the esophagus. UES is one of two sphincters in the GI tract that are composed of striated muscle.

Tonic Contraction

maintained contraction without relaxation sustained for hours, serve to prevent chyme from moving freely from one organ to another the lower esophageal, pyloric, ileocecal, and internal anal sphincters.

Regulation of the strength and pattern of smooth muscle contractions

oSpontaneous electrical activity in the plasma membrane of muscle cells. oNeurotransmitters released by autonomic neurons. oHormones oLocally induced changes in the chemical composition (paracrine agents, acidity, oxygen, osmolality, and ion concentrations) of the extracellular fluid surrounding muscle cells oStretch

Trypsin is made by

pancreas

Esophageal phase of swallowing

phase in which esophageal peristalsis carries the bolus through the esophagus and LES and into the stomach Esophageal phase requires neural coordination of skeletal and smooth muscle contractions UES relaxes and closes when food is passed The esophagus advances food toward the stomach using skeletal muscle (upper 1/3rd) and smooth muscle (lower 2/3rd), the latter generating peristaltic contractions Peristaltic waves propel food toward the LES (takes about 9 sec) LES opens to allow passage of food into stomach

Smooth muscle sphincters involuntarily:

regulate filling and emptying of the different regions of the intestinal tract.

Lower esophageal sphincter (LES)

relaxes as food reaches the bottom of the esophagus. In addition, LES blocks retro-entry of chyme from the stomach into the esophagus. However, LES can lose it contractility, and chyme and acid entering esophagus cause gastroesophageal reflux disease (GERD) or heartburn.

Striated muscle sphincters allow voluntary control of:

the entrance of food into the GI tract (UES). the exit of food (external anal sphincter).

Gastric motility

•As food enters the stomach the smooth muscles in the wall relax to accommodate the volume w/o increasing the pressure (reservoir function).

Potential oscillations are produced by fluctuating channel activation

Depolarization during slow waves, activates voltage-gated Ca++ channels and increases intracellular Ca++ which further depolarize cells without inducing an action potential. If the threshold is reached, the additional Ca++ influx produces a stronger contraction. Increased intracellular Ca++ activates Ca++-dependent K+ channels which repolarize the cells and the Ca++ decreases. Decreased Ca++ turns off the K+ channels and allows the cells the slowly depolarize again. These events are presented graphically in the following slide.

Defecation reflex:

Distension of rectum following a mass movement relaxes the internal sphincter initially, and then if pressure continues, the external sphincter. If defecation is not desired, voluntary control can override relaxation of the external sphincter and keep external sphincter closed. Under voluntary closure, the contents of the rectum are returned to the sigmoid colon by reverse peristalsis. The urge to defecate subsides until the next mass movement

Anus (exit from rectum) is normally closed by:

Internal anal sphincter composed of smooth muscle involuntary control External anal sphincter composed of striated skeletal muscle voluntary and involuntary control

Large Intestinal motility

Mixing movements (haustrations) Slower than in small intestine. Food remains 18-24 hrs. Slow propulsion toward anus. Propulsive movements (mass movements) Occur 3 to 4 times a day usually stimulated by eating. They are sustained peristaltic contractions of the transverse colon. Movement of chyme into rectum stimulates defecation reflex.

Intestinal motility

Peristalsis: Rhythmic wave of smooth muscle contraction that results in the propulsion Mixing contraction: During meal digestion, the predominant contractions in the small intestine are segmenting and clustered. mix contents propel contents slowly

External anal sphincter:

The external anal sphincter is made up exclusively of striated muscle and is under involuntary and voluntary control. If the internal sphincter has relaxed, the external sphincter will also relax as part of the defecation reflex. Voluntary neural inputs can override this reflex and keep the external sphincter contracted.

Internal anal sphincter:

The internal anal sphincter is composed of smooth muscle and is under involuntary control. Increased pressure in the rectum produced by a mass movement relaxes the internal sphincter.

Latch Mechanism

The latch mechanism facilitates prolonged holding of smooth muscle contraction. The latch state occurs when a phosphorylated cross-bridge becomes dephosphorylated while still attached to myosin. In this state it can maintain tension in an almost rigor-like state without movement. This mechanism allows static tension to be maintained for long periods with very little use of ATP. This mechanism is used in sphincter muscles in the GI tract.

Pyloric sphincter:

The pyloric sphincter is composed of smooth muscle and is under involuntary control. Motility of the stomach and contraction of the pyloric sphincter are regulated together. Increased motility is correlated with increased contraction of the pyloric sphincter.

The rate of stomach emptying depends upon the nature of the meal consumed

This is a comparison of stomach emptying between solid and liquid meals. The transit time varies depending on types of food ingested. Liquid food moves through the GI tract faster as this does not require much time for mechanical breakdown. In comparison, solid food and fatty food will require more time for mechanical breakdown and absorption.

Types of smooth muscle contraction and location of each type in the GI tract

Tonic Phasic

There are two types of smooth muscle contraction in the GI tract.

Tonic contractions occurs where smooth muscle fibers remain contracted over many minutes or hours. All the sphincters undergo this type of contraction to retain chyme in one chamber and prevent it from emptying into the next without giving sufficient time for digestion and absorption. Phasic contraction is rhythmic contraction that occurs in the esophagus, the body of the stomach, small intestine, and colon where this breaks down food/chime into smaller particles and advance chime aborally.

How long does digestion and absorption take?

Transit times in healthy humans following ingestion of a standard meal (i.e. solid, mixed foods). •50% of stomach contents emptied 2.5 to 3 hours •Total emptying of the stomach 4 to 5 hours •50% emptying of the small intestine 2.5 to 3 hours •Transit through the colon 18 to 35 hours

The GI tract wall is composed of smooth muscles.

Unlike skeletal muscle that contracts in one direction, smooth muscle can contract in multi-directions. Also, while skeletal muscles contact and relax rapidly, most smooth muscle contraction is slow and prolonged. Smooth muscle lack the striated arrangement of actin and myosin filaments of skeletal muscle. Instead, large numbers of actin filaments are attached to dense bodies. Some of these bodies are attached to the cell membrane and others are dispersed inside the cell.

Vomiting reflex

Vomiting is the forceful expulsion of the contents of the stomach and upper intestinal tract through the mouth. The purpose is to remove ingested toxic substances before they are absorbed. Vomiting is a complex reflex coordinated by the vomiting center in the brainstem medulla oblongata. The vomiting center receives vagal and sympathetic afferents triggered by numerous stimuli in multiple regions of the body.

Gastric motility

•Pacemaker cells (Interstitial cell of Cajal) initiates excitation. Peristaltic waves beginning in the body increase in strength as they progress toward the antrum (gastric pump function). Outer longitudinal and inner circular muscle contract, followed by relaxation. 3 contraction/min.

Action potentials regulate intracellular [Ca++]

•Slow waves of membrane potential are generated by pacemaker cells, interstitial cells of Cajal, in the interstitium of the muscle layers. •Rhythmic depolarization opens voltage-gated Ca++ channels and the increased intracellular calcium induces some contraction. •Further depolarization above the threshold potential induces action potential (spike potential), producing contractions. •The intensity of contractions is proportional to intracellular Ca++.

•The pyloric sphincter closes to allow only a small volume of chyme to enter the duodenum.

•The remainder is forced back into the body and thoroughly mixed. •Motility is controlled by hormonal and neural feedback from duodenum to slow down when duodenum is distended, high fat, high acid, and hypertonicity. •In the fasting state, stomach is relaxed with brief intervals of activity known as the migrating motor complex (MMC; peristaltic waves that propel remaining contents into the large intestine).

The migrating motor complex (MMC)

•a special type of peristaltic contraction that sweep through the intestine in a regular cycle during fasting state •MMC begins in lower stomach and proceed slowly to the ileum over 2 hours and ends at the ileocecal sphincter. •MMC ceases when the next meal enters the stomach •MMC is controlled by ENS and the hormone motilin •MMC serves to load chyme from last meal into proximal colon in order to prepare the small intestine for the next meal (a housekeeping function) •It causes growling of the stomach between meals. Associated with discomfort "hunger pain".

Chewing is controlled by the somatic nerves to the skeletal muscles of the mouth and jaw. Swallowing is a complex reflex controlled by the swallowing center in the medulla oblongata of the brain stem. It is initiated when pressure receptors in the walls of the pharynx are stimulated by food or drink forced into the rear of the mouth by the tongue.

(a) Tongue pushes food bolus to back of pharynx (b) Soft palate elevates to prevent food entering the nasal passages (c) Epiglottis covers glottis to prevent food from entering the trachea (d) Upper esophageal sphincter relaxes