Electrical & Mechanical Properties.p.ptx

Physiology

1. Electrical & Mechanical Properties of GIT Smooth Muscles Kamran

2. GI Smooth Muscle Functions as a Syncytium The individual smooth muscle fibers in the GI tract are 200 to 500 μ m in length and 2 to 10 μ m 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 and help to travel electrical signals more readily in the longitudinal direction than sideways

3. Each bundle of smooth muscle fibers is partly separated from the next by loose connective tissue However, the muscle bundles fuse with one another at many points, thus, representing a branching latticework of smooth muscle bundles This makes the muscle layer a syncytium, i.e., 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 mm, and at other times it travels many cm or even the entire length and breadth of the intestinal tract A few connections also exist between the longitudinal and circular muscle layers, excitation of one of these layers often excites the other as well

4. GI Smooth Muscle: Circular Muscle and Longitudinal Muscle Longitudinal Muscle Thin Muscle Coat Contraction shortens intestine length & expands radius Innervated & activated by excitatory motor neurons Few gap junctions to adjacent fibers Extracellular Ca 2+ influx important in excitation-contraction coupling Circular Muscle Thick Muscle Coat Contraction increases intestine length & decreases radius Innervated by excitatory & inhibitory motor neurons Activated by myogenic pacemaker & excitatory motor neurons Many gap junctions to adjacent fibers Intracellular Ca 2+ release important in excitation-contraction coupling

5. Electrical Activity of GI Smooth Muscle Normal GI motility results from coordinated contractions of smooth muscles, which in turn derives from 2 basic pattern of electric activity across the membranes of smooth muscle cells: Slow waves and spike potentials The RMP of smooth muscle cells (SMCs) varies between -50mV to -60mV which fluctuates spontaneously These fluctuations spread to adjacent sections of muscle as the muscle cells are electrically coupled and results in what are called “slow waves”- waves of partial depolarization in smooth muscle that sweep along the digestive tube for long distances

6. These fluctuations are equivalent to fluctuations in membrane potential of 5-15 mV. The frequency of slow waves is from 3 to 12/min and depends on the section of digestive tube- about 3 in the body of the stomach, up to 12 in the duodenum & about 8 or 9 in the terminal ileum Slow wave activity appears to be a property intrinsic to smooth muscle and not dependent on nervous stimuli Slow waves appear to be caused due to specialized cells, called the interstitial cells of Cajal (ICC) , that are believed to act as electrical pacemakers for smooth muscle cells

7. The ICC form a network with each other and are interposed between the smooth muscle layers, with synaptic-like contacts to smooth muscle cells The ICC undergo cyclic changes in membrane potential due to unique ion channels that periodically open and produce inward (pacemaker) currents that may generate slow waves Slow waves are not action potentials and by themselves do not elicit contractions Rather, they coordinate or synchronize muscle contractions in the gut by controlling the appearance of a 2 nd type of depolarization event- ‘spike potential’ which occur only at the crest of slow waves

8. SPIKE POTENTIAL: The spike potentials are true action potentials that elicit muscle contractions It results when the RMP of the GI smooth muscle becomes more positive than about −40 millivolts When a slow wave passes over an area of smooth muscle that has been primed by exposure to neurotransmitter (NT) released in their vicinity by neurons of ENS, the peak of the slow waves temporarily become more positive than −40 millivolts, and spike potential appears on this peak NTs are released in response to a variety of local stimuli, including distension of the wall of digestive tube and serve to sensitize the muscle by making its RMP more positive

9. The higher the slow wave potential rises, the greater the frequency of the spike potentials, usually ranging between 1 and 10 spikes per second GI spike lasts as long as 10 to 20 milliseconds In GI smooth muscle fibers, the channels responsible for the action potentials are calcium-sodium channels which allow large numbers of calcium ions to enter along with smaller numbers of sodium ions Ca 2+ , acting through a calmodulin control mechanism, cause sliding of actin over myosin filament, thus, leading to muscle contraction

10. Factors for RMP in GI Smooth Muscles The average RMP of GI smooth muscle is -56 mV which is subjected to change by multiple factors When the potential becomes less negative, the muscle fibers become more excitable When the potential becomes more negative, 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 Factors that cause hyperpolarization of 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

11. GI Motility In the human GIT, the muscles in the proximal two- third of the esophagus and in the external anal sphincter are skeletal; the rest of the muscularis contain smooth muscles GI smooth muscles are autonomus - generating spontaneous electrical rhythmicity and contractions driven by intrinsic pacemakers, Ca 2+ handling and Ca 2+ sensitization mechanisms The contraction of smooth muscles cells independently or as a syncytium is not sufficient to produce GI motility patterns and orderly progression of luminal contents

12. Multiple levels of regulatory cells and mechanisms including interstitial cells, motor neurons, hormone, paracrine substances and inflammatory mediators are superimposed by myogenic activity to generate normal and abnormal contractile behavior The smooth muscle tissue of the GIT are not homogenous and hence differences in electrical and mechanical activities exist in different regions of GIT and in the sphincters separating these regions

13. Multiple levels of regulatory cells and mechanisms including interstitial cells, motor neurons, hormone, paracrine substances and inflammatory mediators are superimposed by myogenic activity to generate normal and abnormal contractile behavior The smooth muscle tissue of the GIT are not homogenous and hence differences in electrical and mechanical activities exist in different regions of GIT and in the sphincters separating these regions Role of Ca 2+ in GI Motility Steps involved in smooth muscle cell contraction: Calcium entry into smooth muscle fibers occurs: via activation of voltage dependent Ca 2+ channels ( L-type voltage-gated calcium channels) as a result of SMCs depolarization byhormone / NT activation via nonselective cation channels activated by 2 nd messengers due to agonist stimulation or by stretch or via Transient receptor potential (TRP) channels (voltage-independent channels activated either by intracellular Ca2+ or by G-protein coupled mechanism)

14. Calcium-induced calcium release from the SR Increased intracellular calcium Calmodulin binds calcium Myosin light chain kinase activation Phosphorylation of myosin light chain Increase Myosin ATPase activity Myosin-P binds Actin  Cross-bridge cycling leads to muscle tone Dephosphorylation of myosin light chains terminates smooth muscle contraction Myosin light chain phosphatase (MLCP) is responsible for dephosphorylation of the myosin light chains ultimately leading to smooth muscle relaxation .

15. Intrinsic activity & Ca 2+ entry 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

16. Types of Contractions in GIT Phasic contractions - periodic contractions followed by relaxation; such as in gastric antrum , small intestine and esophagus Tonic contractions - contractile tension that is maintained for prolonged periods of time without relaxation; such as in orad region of stomach, in lower esoghageal , ileocecal and internal anal sphincter; exhibited by some smooth muscles of GIT - not associated with slow waves Caused by: Continuous repetitive spike potential Hormonal effects Continuous entery of Ca

17. BASIC PATTERNS OF GI MOTILITY Motility in the digestive tract accounts for the propulsion, mixing, and reservoir functions necessary for the orderly processing of ingested food and the elimination of waste products Two types of movements occur in the GIT: Propulsive movements, which cause food to move forward along the tract at an appropriate rate to accommodate digestion and absorption, and Mixing movements , which keep the intestinal contents thoroughly mixed at all times Reservoir functions are performed by the stomach and colon

18. PROPULSIVE MOVEMENTS—PERISTALSIS The basic propulsive movement of the GIT is peristalsis, A contractile ring appears around the gut and then moves forward; this mechanism is analogous to putting one’s fingers around a thin distended tube, then constricting the fingers and sliding them forward along the tube Any material in front of the contractile ring is moved forward Peristalsis is an inherent property of many syncytial smooth muscle tubes Stimulation at any point in the gut can cause a contractile ring to appear in the circular muscle, and this ring then spreads along the gut tube

19. Peristalsis also occurs in the bile ducts, glandular ducts, ureters, and many other smooth muscle tubes of the body The usual stimulus for intestinal peristalsis is distention of the gut, i.e., if a large amount of food collects at any point in the gut, stretching of the gut wall stimulates the ENS to contract the gut wall 2 to 3 centimeters behind this point, and a contractile ring appears that initiates a peristaltic movement Other stimuli that can initiate peristalsis include chemical or physical irritation of the epithelial lining in the gut Also, strong parasympathetic nervous signals to the gut will elicit strong peristalsis

20. When a segment of the intestinal tract is excited by distention and thereby initiates peristalsis, the contractile ring causing the peristalsis normally begins on the orad side of the distended segment and moves toward the distended segment, pushing the intestinal contents in the anal direction for 5 to 10 centimeters before dying out At the same time, the gut sometimes relaxes several centimeters downstream toward the anus, which is called “receptive relaxation,” thus allowing the food to be propelled more easily toward the anus than toward the mouth The peristaltic reflex plus the anal direction of movement of the peristalsis is called the “law of the gut”

21. SEGMENTATION CONTRACTIONS— MIXING MOVEMENTS Mixing movements differ in different parts of the alimentary tract In some areas, the peristaltic contractions cause most of the mixing This is especially true when forward progression of the intestinal contents is blocked by a sphincter so that a peristaltic wave can then only churn the intestinal contents, rather than propelling them forward At other times, local intermittent segmentation contractions occur every few centimeters in the gut wall

22. These constrictions usually last only 5 to 30 seconds; new constrictions then occur at other points in the gut, thus “chopping” and “shearing” the contents first here and then there These peristaltic and constrictive movements are modified in different parts of the gastrointestinal tract for proper propulsion and mixing

23. Motility in Different Parts of GIT Mouth and Esophagus: Chewing, Swallowing, Peristalsis Stomach: Filling, Churning, Peristalsis, Emptying Small Intestine: Segmental Contractions, Peristalsis Large Intestine: Haustral Shuttling, Mass Movements, Defecation Sphincters: Regulation of Movement

24. HORMONAL CONTROL OF GI MOTILITY The GI hormones are released into the portal circulation and exert physiological actions on target cells with specific receptors for the hormone The effects of the hormones persist even after all nervous connections between the site of release and the site of action have been severed They are involved in GI secretion but many of them also control gastric motility Secretory functions of hormones are more important than motility functions

25. CCK hormone strongly contracts the gallbladder, expelling bile into the small intestine CCK also inhibits stomach contraction moderately Secretin has a mild effect on motility of the GIT and acts to promote pancreatic secretion of bicarbonate GIP has a mild effect in decreasing motor activity of the stomach and slows gastric emptying Motilin is released cyclically from stomach & upper duodenum and stimulates waves of GI motility called interdigestive myoelectric complexes that move through the stomach and small intestine every 90 minutes in a person who has fasted