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YEDITEPE UNIVERSITY PHYSIOLOGY LECTURES Smooth Muscle Physiology Professor Burcu GEMİCİ BAŞOL Istanbul, 2024 GOALS - TO EXPLORE THE STRUCTURE OF SMOOTH MUSCLE, TYPES OF SMOOTH MUSCLE UNDERSTAND THE FUNCTION OF SMOOTH MUSCLES, - TO EXEMINE THE CONTRACTION AND RELAXATION MECHANISM OF SMOOTH MUSCLES, O...

YEDITEPE UNIVERSITY PHYSIOLOGY LECTURES Smooth Muscle Physiology Professor Burcu GEMİCİ BAŞOL Istanbul, 2024 GOALS - TO EXPLORE THE STRUCTURE OF SMOOTH MUSCLE, TYPES OF SMOOTH MUSCLE UNDERSTAND THE FUNCTION OF SMOOTH MUSCLES, - TO EXEMINE THE CONTRACTION AND RELAXATION MECHANISM OF SMOOTH MUSCLES, OMPARE THE SKELETAL MUSCLE AND SMOOTH MUSCLE TYPES SMOOTH MUSCLE Many of the basic muscle properties are highly modified in smooth muscle, because of the very different functional roles it plays in the body. smooth muscle is an integral component of the SMOOTH MUSCLE PHYSIOLOGY Gastrointestinal canal “Major component of hollow orga Respiratory air ways Urogenital tract PROPERTIES OF SMOOTH MUSCLE While there are major differences among the organs and systems in which smooth muscle plays a major part, the structure of smooth muscle is quite consistent at the tissue level and even more similar at the cellular level. High metabolic economy of smooth muscle! Allows it to remain contracted for long periods with little energy consumption! Small size of smooth muscle cells, Allows precise control of very small structures, (such as blood vessels.) Circular Organization: (Blood Vessels) The simplest smooth muscle arrangement is found in the arteries and veins of the circulatory system. Shortening of the fibers results in reducing the vessel’s diameter (vasocontraction). This circular arrangement is also prominent in the airways of the lungs and also in sphincters. THE PROPERTIES OF SMOOTH MUSCLE Underdeveloped sarcoplasmic reticulum (SR) (contains SR but very primitive one)  Contains thin and thick filaments but, no specific sarcomere structure  Centrally located nucleus  NO T-tubule (Transvers tubule)!  NO troponin complex! NO neuromuscular junction! The internal physical arrangement of TYPES OF SMOOTH MUSCLE The smooth muscle of each organ is distinctive from most other organs in several ways, (1) physical dimensions, (eye-stomach) (2) organization into bundles or sheets, (3) response to different types of stimuli, (4) characteristics of innervation, (5) function Smooth muscle can generally be divided into two major types, * multiunit smooth muscle and * unitary (or single-unit) smooth muscle. Phasic smooth muscle contracts transiently when stimulated. Examples include muscles that make up the walls of the GI tract (stomach, small intestine, large intestine), and urogenital tract (ureters, urinary bladder, vas deferens, fallopian tube, uterus). Tonic smooth muscle is capable of sustained contractions, a feature that is often used to maintain a constant muscular tone. Examples include vascular and airway muscle, sphincters (e.g., lower esophageal sphincter, pyloric sphincter), and eye ciliary and iris muscles. nitary (PHASIC) Smooth Muscle *a mass of hundreds to thousands of smooth muscle fibers that contract together as a single unit. *arranged in sheets or bundles, and their cell membranes are adherent to one another at multiple points so that force generated in one muscle fiber can be transmitted to the next. *The cell membranes are joined by many gap junctions through which ions can flow freely from one muscle cell to the next. Unitary Smooth Muscle Have extensive intercellular electrical communication This type of smooth muscle is also known as syncytial smooth muscle because of its syncytial interconnections among fibers. called visceral smooth ltiunit (TONIC) Smooth Muscle. *Composed of discrete, separate smooth muscle fibers. *Each fiber operates independently of the others *Each fiber is innervated by a single nerve ending, as occurs for skeletal muscle fibers. *The outer surfaces of these fibers, are covered by a thin layer of basement membrane–like substance, a mixture of fine collagen and glycoprotein that helps insulate the separate fibers from one another. *The most important characteristic of multi-unit smooth muscle fibers is that each fiber can contract independently NO T-tubule (Transvers tubule)!  NO troponin complex! NO neuromuscular junction! Caveolae instead of T-tubule Calmodulin instead of Troponin complex *Keeps calcium close to the membrane. Varicosites instead neuromuscular junction Neuromuscular junctions of the highly structured type found on skeletal muscle fibers do not occur in smooth muscle. Instead, the autonomic nerve fibers that innervate smooth muscle generally branch diffusely on top of a sheet of muscle fibers. VARICOSITES Varicosites instead of neuromuscular junction What are varicosities? Expanded axon parts or, numerous bulbous swellings in smooth muscle; release neurotransmitter into a wide synaptic cleft in the general area of the smooth muscle cells. Such junctions are called diffuse junctions Is smooth muscle Excitatory, Inhibitory, or Both? HOW? (Please remember, skeletal muscle is only Excitatory!) Excitatory and Inhibitory Transmitter Substances Secreted at the Smooth Muscle Neuromuscular Junction (varicosites) The most important transmitter substances secreted by the autonomic nerves innervating smooth muscle are acetylcholine and norepinephrine, but they are never secreted by the same nerve fibers. Acetylcholine is an excitatory transmitter substance for smooth muscle fibers in some organs but an inhibitory transmitter for smooth muscle in other organs. When acetylcholine excites a muscle fiber, norepinephrine ordinarily inhibits it. Conversely, when acetylcholine inhibits a fiber, norepinephrine usually excites it. But why are these responses different? The answer is that both acetylcholine and norepinephrine excite or inhibit smooth muscle by first binding with a receptor protein on the surface of the muscle cell membrane. Some of the receptor proteins are excitatory receptors, whereas others are inhibitory receptors. Thus, the READ MEtype  INNERVATION A smooth muscle cell may receive input from more than one neuron * NO the same striated arrangement of actin and myosin filaments similar with skeletal muscle. Instead, large numbers of actin filaments attached to structure called dense bodies. (dense bodies are The functional equivalents of the Z lines) *Some of dense bodies are attached to the cell membrane. *Others are dispersed inside the cell. *Some of the membrane-dense bodies of adjacent cells are bonded together by intercellular protein bridges. It is mainly through these bonds that the force of contraction is Cell-to-Cell Contacts Smooth muscle cells are connected to each other 1.Gap junctions – Low-resistance pathways – Action potentials can readily propagate 2.Adherens junctions (dense bodies) – Provide mechanical linkage – Thin filaments extend into the adherens junction CONTRACTILE MECHANISM IN SMOOTH MUSCLE *Contains actin and myosin filaments, *Chemical characteristics of actin and myosin filaments similar within skeletal muscle, interact with each other in much the same way that they do in skeletal muscle. *No troponin complex, so the mechanism for control of contraction is entirely different. *The contractile process is activated by calcium ions, and adenosine triphosphate (ATP) is degraded to adenosine diphosphate (ADP) to provide the energy for contraction. *Major differences between the physical organization of smooth muscle and that of skeletal muscle, as well as differences in excitation-contraction coupling, control of the contractile process by calcium ions, duration of contraction, and amount of energy required for contraction. Major Routes Of Calcium Entry And Exit From The Cytoplasm Of Smooth Muscle CONTRACTION OF SMOOTH MUSCLE CONTRACTI LE MECHANISM IN SMOOTH MUSCLE COMPARISION OF SMOOTH AND SKELETAL MUSCLE CONTRACTION MECHANISM Major Routes Of Calcium Entry And Exit From The Cytoplasm Of Smooth Muscle CONTRACTION OF SMOOTH MUSCLE Source of Calcium Ions In smooth muscle there is a few slightly developed sarcoplasmic tubules. (Instead Caveolae) Smooth muscle contraction ıs dependent on extracellular calcium ıon concentration. A calcium pump is required to cause smooth muscle relaxation. RELAXATION OF SMOOTH MUSCLE CONTRACTI ON MECHANIS MS OF SKELETAL AND SMOOTH MUSCLES Smooth Contraction is thick filament regulated Contract in respons to electrical and hormonal Single/multi unit Autonomic nervous system Thick muscle cells Caveola Dens body Varicosites Striated Contraction is thin filament regulated Contract in respons to electrical stimulus Fast/slow Somatic nervous system Thin muscle cells T Tubules Z lines Neuromuscular junctions Activation of Smooth Muscle Contraction; Chemical factors control the function of smooth muscle cells Some factors act by opening or Others result in production of a closing cell membrane ion second messenger that diffuses to the interior of the cell, where it channels. causes further changes. The final result of both mechanisms is usually a change in the intracellular concentration of Ca, which, in turn, controls the contractile process itself. Membrane Potentials and Action Potentials in Smooth Muscle Membrane Potentials in Smooth Muscle The quantitative voltage of the membrane potential of smooth muscle depends on the momentary condition of the muscle. In the normal resting state, the intracellular potential is usually about −50 to −60 millivolts. (which is about 30 millivolts less negative than in skeletal muscle.) Action Potentials in Unitary Smooth Muscle Action potentials occur in unitary smooth muscle (such as visceral muscle) in the same way that they occur in skeletal muscle. The action potentials of visceral smooth muscle occur in one of two forms: (1) spike potentials or (2) action potentials with plateaus. 1 2 3 Typical spike action potentials Typical spike action potentials, such as those seen in skeletal muscle, occur in most types of unitary smooth muscle. The duration of this type of action potential is 10 to 50 milliseconds. Such action potentials can be elicited in many ways, for example, * by electrical stimulation, * by the action of hormones on the smooth muscle, * by the action of transmitter substances from nerve fibers, The resting potential of most smooth muscles is approximately * by stretch, or as a result of 50 mV. This is less negative than the resting potential of nerve spontaneous generation in the muscle and other muscle types, it is determined primarily by the fiberion itself, transmembrane potassium gradient. The smaller potential (-50 mV) is due primarily to a greater resting permeability to sodium ions. 3.Slow Wave Potentials in Unitary Smooth Muscle Can Lead to Spontaneous Generation of Action Potentials. Some smooth muscle is selfexcitatory. That is, action potentials arise within the smooth muscle cells themselves without an extrinsic stimulus. This is often associated with a basic slow wave rhythm of the *The slow wave itself is not the membrane potential. action potential. *The importance of the slow waves is that, when they are strong enough, they can initiate action potentials. The slow waves themselves cannot cause muscle contraction. A typical slow wave in a visceral smooth muscle of the gut Electrical slow-wave frequencies; Slow waves with similar waveforms occur at different frequencies in the stomach, small intestine, and colon. In many smooth muscles, the resting potential varies periodically with time, producing a rhythmic potential change called a slow wave. Effect of Local Tissue Factors and Hormones to Cause Smooth Muscle Without Actionpotential Potentials TwoContraction types of non-nervous and nonaction stimulating factors often involved are (1) local tissue chemical factors and (2) various hormones. 1.Lack of oxygen in the local tissues causes smooth muscle relaxation and, therefore, vasodilatation. 2.Excess carbon dioxide 3.Increased hydrogen concentration Adenosine, lactic increased potassium diminished calcium ion acid, ions, ion Many circulating hormones in the blood affect smooth muscle contraction 1.norepinephrine, 2.epinephrine, 3.acetylcholine, 4.angiotensin, 5.endothelin, 6.vasopressin, 7.oxytocin, 8.serotonin, 9. histamine. SUMMARY The primary step in the regulation of smooth muscle contraction is the phosphorylation of the regulatory light chains of the myosin molecule, which is then free to interact with actin. Relaxation involves phosphatase-mediated dephosphorylation of the light chains. The contractions of smooth muscle are considerably slower than those of skeletal muscle, but are much more economical in their use of cellular energy. Good luck 

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