Physiology of Smooth

Lecture title: Physiology of smooth muscles Date:22/12/2021 Types of smooth muscles: B. Multiunit smooth muscle  Require individual nerve innervation (no pacemaker activity)  Few or no gap junctions  They behave a separate motor units  They are composed of discrete, separate smooth muscle fibers  Each muscle operates independently of the others  They are innervated by a single nerve ending, as for skeletal muscle fibers  they are similar to skeletal muscle than to visceral smooth muscle  They are densely innervated; contraction is controlled and activated by neural innervations (e.g., autonomic nervous system). Copyright © 2021 by Saunders, an imprint of Elsevier Sheet Note 1 Types of smooth muscles: A. Unitary (single-unit) smooth muscle:Group of smooth muscle fibers that act as one unit. AP can travel from one fiber to the next throw multiple gap junctions causing muscle fibers contraction (pacemaker activity). B. Multiunit smooth muscle Continue …… They don’t not contract spontaneously They are found in places where fine control of contraction is needed such as respiratory airways and large arteries. Examples: the ciliary muscle (the muscle that focuses the eye), the iris muscle of the eye the piloerector muscles that cause erection of the hairs when stimulated by the sympathetic nervous system. Copyright © 2021 by Saunders, an imprint of Elsevier Sheet Note 2 • • • Multiunit smooth muscles need an AP in order to contract. Smooth muscles are innervated by Autonomic nervous system. Most of the smooth muscles are unitary and only few of them are multiunit. Smooth muscle electrical activity A. Unitary (visceral) smooth muscle:  When unitary smooth muscle is stretched sufficiently, spontaneous action potentials usually are generated. They result from a combination of: (1) The normal slow wave potentials and (2) The decrease in overall negativity of the membrane potential caused by the stretch itself.  Resting membrane potential: unstable resting membrane potential (-55 to -35 mV)  Action potential (AP):  When depolarization reaches threshold potential, an AP is generated and will be transmitted to the adjacent muscle through the gap junction.  Some smooth muscles are self-excitatory  AP arise within the smooth muscle cells without an extrinsic stimulus. Represent AP Copyright © 2021 by Saunders, an imprint of Elsevier Sheet Note 3 • • • • • • AP in smooth muscles is activated by hormones, neurotransmitters, chemicals and stretching . Threshold potential = -35 mV. The activation of the parasympathetic system(rest and digest) causes activation of the smooth muscles . The activation of the sympathetic system(fight and flight) causes inhibition of the smooth muscles . Epinephrine and norepinephrine secreted from sympathetic system. Acetylcholine secreted from the parasympathetic system . Types of membrane potential: 1. Slow wave potential:  can lead to spontaneous generation of AP if they are strong It is seen in a visceral smooth muscle of the gut. Slow wave each peak one or more action potentials occur. The repetitive sequences of AP elicit rhythmical contraction of the smooth muscle mass the slow waves are called pacemaker waves Smooth muscle action potential A. Electrical activity of unitary (visceral) smooth muscle:-… continue 2. Spike potential: It is similar to that seen in skeletal muscle It is observed in most single unite smooth muscle It is average duration (10 to 50 msec), with very low amplitude. It is stimulated by electrical, hormonal, neurotransmitters, and stretch 3. Action potential with plateau  Seen in ureter and some vascular smooth muscle.  Started as rapid depolarization and delayed repolarization (100 to 1000 msec)  The importance of the plateau is that it can account for the prolonged contraction that occurs in some types of smooth muscle (ureter and certain types of vascular smooth muscle) Ionic basis of action potential  In smooth muscle the depolarization is due to entry of Ca and not Na  entry of Ca relate to contraction and explain the prolonged AP Copyright © 2021 by Saunders, an imprint of Elsevier Sheet Note 4 • In smooth muscles the depolarization is due to entry of Ca unlike skeletal muscles and neurons that are depolarized due to entry of Na. Smooth muscle action potential B. Electrical activity of multi-unit smooth muscle (without AP)  They normally contract in response to nerve stimuli.  The nerve endings secrete ACh or NE  The neurotransmitter causes depolarization of the smooth muscle membrane, and this depolarization in turn elicits contraction.  AP usually do not develop because the fibers are too small to generate an AP  The local depolarization (junctional potential) caused by the nerve transmitter substance that spread electrotonically over the entire fiber and cause muscle contraction. Copyright © 2021 by Saunders, an imprint of Elsevier Sheet Note 5 • In multi-unit smooth muscle there is no AP but there is postsynaptic membrane potential . Excitation-Contraction Coupling in Smooth Muscle Action potentials a. Begins with rise in intracellular calcium concentrations 1) Only some comes from SR. 2) Most comes across plasma membrane after voltagegated calcium channels are opened. Threshold Voltage-gated Ca2+ channels open in plasma membrane Graded depolarizations Time Ca2+ + calmodulin P MLCK Inactive Calmodulin–Ca2+ complex 1. Phosphorylation of cross bridges leads to contraction MLCK Active b. Calcium binds to calmodulin (no troponin in smooth muscle). 1) Activates myosin light chain kinase (MLCK) Depolarization Membrane potential Cross bridge inactivation and relaxation Myosin light chain Myosin light chain P Cross bridge activation and contraction 2. Dephosphorylation of cross bridges leads to relaxation Myosin phosphatase Active Myosin phosphatase P Inactive Copyright © 2021 by Saunders, an imprint of Elsevier Continue……. Action potentials c.Myosin light chain kinase phosphorylates myosin light chains. 1)This allows myosin to form cross bridges with actin to initiate contraction. d.Stimulation is graded. More stimulation allows in more calcium, which allows stronger contractions. e.Contractions are slow and sustained. 1)May enter a “latch state” Threshold Depolarization Membrane potential Voltage-gated Ca2+ channels open in plasma membrane Graded depolarizations Time Ca2+ + calmodulin P MLCK Inactive Calmodulin–Ca2+ complex 1. Phosphorylation of cross bridges leads to contraction MLCK Active Cross bridge inactivation and relaxation Myosin light chain Myosin light chain P Cross bridge activation and contraction 2. Dephosphorylation of cross bridges leads to relaxation Myosin phosphatase Active Myosin phosphatase P Inactive Copyright © 2021 by Saunders, an imprint of Elsevier Mechanical contraction of smooth muscle  The actin thin filaments are attached to Dense bodies (Instead of Z line)  The intermediate filaments composed of the Desmin protein (maintain structure and mechanical integrity of the contractile apparatus in muscle)  The dense bodies and intermediate filaments anchor the thin filaments when sliding occurs between thin and thick filaments, contraction pull the dense bodies’ together the cell shortens Copyright © 2021 by Saunders, an imprint of Elsevier Sheet Note 6 *the pictures from google Continue ……. Caldesmon and Calponin block the binding site Caldesmon with Tropomyosin, regulate the access of myosin to actin  In relaxed smooth muscle the binning site on myosin is blocked by the Caldesmon-Tropomyosin complex Smooth muscle has less myosin; myosin: actin (1:12) while in striated muscle myosin: actin (1:6) Copyright © 2021 by Saunders, an imprint of Elsevier Continue …….  Myosin filaments have side-polar (cross-bridges arranged)  This arrangement allows the myosin to pull an actin filament in one direction on one side, and at the same time pulling another actin filament in the opposite direction on the other side (allows smooth muscle cells to contract about 80 % of their length compared to about 30 % in skeletal muscle) Myosin is scattered throughout the sarcoplasm of a smooth muscle cell Dense bodies are not arranged in straight lines, so when a contraction occurs, the muscle cell twists like a corkscrew Skeletal muscles Smooth muscles Copyright © 2021 by Saunders, an imprint of Elsevier Excitation-Contraction Coupling in Smooth Muscle 1. Begin with rise in intracellular [Ca ]: A. Most of the Ca that enter cells influx from the extracellular fluid through Ca channels: - The time required for Ca diffusion (200 to 300 msec) before contraction begins is called latent period (it is 50 times more in smooth muscle compared to skeletal muscle contraction) B. Some of the intracellular Ca comes from SR  When AP is transmitted into the caveolae (small invaginations of the cell membrane resembles the T tubule of skeletal muscle)  It excite Ca release from the SR tubules that lie near the cell membrane  When the extracellular fluid [Ca] decreases to less than the normal smooth muscle contraction usually ceases (the force of contraction of smooth muscle is dependent on the extracellular fluid [Ca]) Copyright © 2021 by Saunders, an imprint of Elsevier Excitation-Contraction Coupling in Smooth Muscle 2. The Ca ions bind with Calmodulin  Calmodulin (substitute Troponin) present in large amounts in smooth muscles  It initiates contraction by activating the myosin cross-bridges. 3. Calmodulin-Calcium complex activates myosin light chain Kinase enzyme (MLCK) 4. The MLCK phosphorylates myosin light chains (regulatory chain)  This allows myosin to form cross bridges with actin to initiate contraction.  Stimulation is graded  More stimulation allows in more Ca, which allows stronger contractions.  Contractions are slow and sustained.  When myosin light chain is not phosphorylated, the cross bridge cycle with actin does not occur.  Smooth muscle contraction is regulated by both Ca and myosin light chain phosphorylation. Copyright © 2021 by Saunders, an imprint of Elsevier Relaxation of smooth muscle 1. Ca is removed from the intracellular fluid of smooth muscles a. Ca re-enter the SR by the ATPdependent Ca pump b. Ca is removed out of the cell by ATPdependent Ca pump and by the Na/Ca exchanger protein . 2. Phosphate groups are stripped from the myosin by myosin light chain phosphatase. 3. Calmodulin dissociates from myosin light chain kinase (MLCK) 4. Dissociation of the Ca-Calmodulin complex Copyright © 2021 by Saunders, an imprint of Elsevier Comparison of Smooth Muscle and Skeletal Muscle Contraction (1) Slow Cycling of the Myosin Cross-Bridges in smooth muscles  The speed of attachment of the myosin cross-bridges to actin in smooth muscle is slower than in skeletal muscle  Yet, the time that the cross-bridges remain attached to the actin filaments is more in smooth muscle. (2) Low Energy Requirement to Sustain Smooth Muscle Contraction  The energy that is required to sustain the same tension of contraction in smooth muscle is lower than that in skeletal muscle (because of slow attachment and detachment cycling of the cross-bridges and one molecule of ATP is required for each cycle, regardless of its duration)  This is important to the overall energy economy of the body (intestines, urinary bladder, gallbladder, other viscera maintain tonic muscle contraction indefinitely) (3) The Maximum Force of Contraction Is Greater in Smooth Muscle Than in Skeletal Muscle  Results from the prolonged period of attachment of the myosin cross-bridges to the actin filaments in smooth muscles Copyright © 2021 by Saunders, an imprint of Elsevier Sheet Note7 • • Cycling of the Myosin Cross-Bridges maintain the contraction of the muscle. Cycling of the Myosin Cross-Bridges stopped when relaxation process started. Continue….. (4) Slow Contraction and Relaxation of the Total Smooth Muscle Tissue Most skeletal muscles contract and relax rapidly, while smooth muscle contraction is prolonged tonic contraction that may last hours to days  smooth muscle tissue begins to contract (latent period) 50 to 100 msec after it is excited, reaches full contraction about 0.5 second later, and then declines in contractile force in another 1 to 2 seconds, giving a total contraction time of 1 to 3 seconds (about 30 times longer than skeletal muscle fiber) The slow onset of contraction of smooth muscle, as well as its prolonged contraction, is caused by the slowness of attachment and detachment of the cross-bridges with the actin filaments, also the initiation of contraction in response to Ca ions is much slower than in skeletal muscle Copyright © 2021 by Saunders, an imprint of Elsevier Continue….. (5) The “Latch” Mechanism Facilitates Prolonged Holding of Contractions of Smooth Muscle  Contractions are slow and sustained in smooth muscles May enter a latch state (lock)  Latch mechanism maintains prolonged tonic contraction in smooth muscle for hours with little use of energy.  When the myosin kinase and myosin phosphatase enzymes are strongly activated  the cycling frequency and contractions are great  as the activation of the enzymes decreases, the cycling frequency decreases  at the same time, the deactivation of these enzymes allows the myosin heads to remain attached to the actin filament for a longer proportion of the cycling period (the number of myosin heads attached to the actin filament remains large) Copyright © 2021 by Saunders, an imprint of Elsevier Continue….. (6) Plasticity of smooth muscles (Stress-relaxation of smooth muscle)  The visceral unitary type of smooth muscle has the ability to return to its original force of contraction very quickly after elongation or shortening Example; The sudden increase in fluid volume in the urinary bladder stretching the smooth muscle in the bladder wall  large increase in pressure in the bladder  However, during the next 15-60 sec, the pressure returns back to the original level when the volume is increased by another step, the same effect occurs again  Conversely, when the volume is suddenly decreased  the pressure falls drastically at first but then rises to the original level  These phenomena are called stress-relaxation and reverse stress-relaxation  This allow hollow organ to maintain the same amount of pressure inside its lumen despite the change in fluid volume Copyright © 2021 by Saunders, an imprint of Elsevier Continue….. Table summarizes the differences between the skeletal and smooth muscles Copyright © 2021 by Saunders, an imprint of Elsevier