Smooth Muscle Physiology PDF

Smooth Muscle Physiology Smooth muscle – structure – locations – regulation of contraction/relaxation – all mainly presented as how smooth muscle contrasts to skeletal muscle Mary Beth Brown UW DPT REHAB 521 Pathophysiology ...

Smooth Muscle Physiology Smooth muscle – structure – locations – regulation of contraction/relaxation – all mainly presented as how smooth muscle contrasts to skeletal muscle Mary Beth Brown UW DPT REHAB 521 Pathophysiology  Overview of Muscle Types Muscles Involuntary Voluntary – Skeletal Striated muscles Attached to bone and control movement – Cardiac muscles Found in the heart, responsible for pumping blood – Smooth muscle Primary muscles of  Smooth Muscle: General Characteristics Not arranged in sarcomeres so not striated – But does contains actin and myosin Spindle shaped with one centrally placed nucleus Commonly found arranged in clusters of cells Innervated by the autonomic nervous system (not somatic) Under involuntary control Can be inhibited and excited  Differences btwn Skeletal and Smooth Compared muscle to skeletal (and cardiac) muscle, smooth muscle: Contract and relax more slowly May change their contractile activity in the absence of changes in membrane potential Can maintain tension for prolonged periods of time Can be activated by stretch Develop active tension over a greater range of muscle lengths Manipulating smooth muscle contraction and relaxation is key in management of many pathologies we discuss in this course!  Location of Major Types of Smooth Muscle Note that most Vascular: blood vessel walls smooth muscle Gastrointestinal: walls of is organized in sheets digestive tract Urinary: walls of bladder & ureters Respiratory: airway passages Reproductive: uterus in females Ocular : eye (ciliary and iris muscle) Smooth muscle Two types of smooth muscle – Multiunit and single unit (AKA visceral) Multi-unit Single Unit, AKA ‘Visceral’  Multi-Unit Smooth Muscle Eye Varicosity Neuron Multi-unit permits finer control  Single-Unit Smooth Muscle Autonomic neuron varicosity Small intestine Gap junctions Neuro- transmitter (Ach or Norepineph.) Smooth muscle Receptor cell Permits coordinated control for walls of vessels  Differences btwn Skeletal and Smooth muscle SR are not as developed as in skeletal muscle – Majority of Ca++ required to initiate contraction in smooth muscle comes in from the ECF, not the SR Vesicles near the surface of the cell membrane (caveolae) receive action potential which allows release of Ca++ into the cytosol Differences btwn Skeletal and Smooth muscle Myosin ATPase activity is lower which reduces rate of cross-bridging and increases duration of eachSkeletal contraction muscle Myosin consists of a continuous chain of Smooth muscle heads which allows for muscle to be Note: myosin heads are in a stretched and continuous chain in smooth muscle lengthened to greater degrees – e.g. the bladder- changes drastically in size as it fills and empties Differences btwn Skeletal and Smooth muscle Nervous Signals Hormonal (Autonomic) Smooth Stimulation Muscle Contraction Local Chemical Stretch of Muscle Conditions Nervous Signals (Somatic) Skeletal muscle Contraction Differences btwn Skeletal and Smooth muscle Nervous Signals Hormonal (Autonomic) Smooth Stimulation Muscle Contraction Local Chemical Stretch of Muscle Conditions Example: Gastric smooth muscle activity for digestion Stimulated by smell of food (nervous signals) Gastrin (a digestion hormone, increases in the circulation with eating) When stomach starts to get full (stretch of muscular walls) When nutrients are detected with digestion (local chemical conditions)  Differences btwn Skeletal and Smooth muscle No NMJ in smooth muscle Depolarization occurs Events that Take Place at the Neuromuscluar Junction Somatic from an increase in motor neuron Ca++ entering the smooth muscle cell Axon terminal rather than an increase in Na+ Ca2+ Ca2+ Action potentials are Action potential ACh Acetyl + choline Voltage-gated Ca2+ channel different, and several Skeletal muscle fiber AChE types possible Motor end Nicotinic plate receptor  Differences btwn Skeletal and Smooth muscle Smooth muscle doesn’t use only NS signaling… circulating neurotransmitters/hormones can also cause e.g. contract/ relax norepinephrine, epinephrine, acetyl- choline, angiotensin, endothelin, vasopressin, oxytocin, serotonin, and histamine Contraction: binding to excitatory receptors Relaxation: binding to inhibitory receptors  Differences btwn Skeletal and Smooth muscle Increased intracellular calcium is required for smooth muscle contraction, just like in skeletal muscle – Skeletal muscle: Calcium binds to TROPONIN C vs. – Smooth muscle: Calcium binds to CALMODULIN How does smooth muscle contract? Increase in cytosolic Ca++ levels from ECF and 1. SR Ca++ binds to Calmodulin 2. Calcium-calmodulin complex binds to and activates the enzyme called myosin-light- 3. chain kinase (MLCK) MLCK phosphorylates light chains in myosin 4. heads (this enhances myosin ATPase activity) Then crossbridge and power stroke for actin and myosin!  Lets Ca++ in from ECF in response to AP 1. Voltage- gated Ca++ 2. IP3-gated channel Ca++ channel Lets Ca++ in from When ECF in response hormone/ to neurotrans- hormone/neuro- mitter transmitter binds, 2nd binding messenger signaling allows Ca++ to be released from the SR 3. Ligand-gated Ca++ channel How does smooth muscle contract? Increase in cytosolic Ca++ levels from ECF and 1. SR Ca++ binds to Calmodulin 2. Calcium-calmodulin complex binds to and activates the enzyme called myosin-light- 3. chain kinase (MLCK) MLCK phosphorylates light chains in myosin 4. heads (this enhances myosin ATPase activity) Then crossbridge and power stroke for actin and myosin! How does smooth muscle contract? Calcium- calmodulin complex How does smooth muscle contract? Activated (phosphorylated) myosin binds with 5. actin to form cross-bridges How does smooth muscle relax? Decrease in intracellular Ca++ inactivates 6. (dephosphorylates) myosin Inactivated myosin releases from cross- bridge 7. Myosin stays loosely attached to actin in ‘Latch-bridges’ which allow for tonic level of tension with little ATP cost See description of latch bridges in Notes  Activated (phosphorylated) myosin binds with 5. actin to form cross-bridges Decrease in intracellular Ca++ inactivates 6. (dephosphorylates) myosin Inactivated myosin releases from cross- bridge 7. Myosin stays loosely attached to actin in ‘Latch-bridges’ which allow for tonic level of tension with little ATP cost See description of latch bridges in Notes Differences btwn Skeletal and Smooth muscle How we regulate contraction force is different in smooth muscle Force largely depends on the relative balance between phosphorylation and dephosphorylation of myosin light chains (MLCs)  Differences btwn Skeletal and Smooth muscle How we regulate contraction force is different in smooth muscle We have a second level of control possible: regulation of Ca++ sensitivity of regulatory proteins, to make it easier or more difficult to contract PKA For example, PKA P phosphorylat es MLCK which ends up inhibiting actin and myosin cross- bridging  What about pathology of Smooth muscle? Multisystemic smooth muscle dysfunction syndrome https://www.act a2alliance.org/ signs-symptom s Disease definition Multisystemic smooth muscle dysfunction syndrome is a rare, genetic, vascular disease characterized by congenital dysfunction of smooth muscle throughout the body, manifesting with cerebrovascular disease, aortic anomalies, intestinal hypoperistalsis, hypotonic bladder, and pulmonary hypertension. Congenital mid-dilated pupils non-reactive to light associated with a large, persistent patent ductus arteriosus are characteristic hallmarks of the disease. What about pathology of Smooth muscle? Vascular: blood vessel walls Gastrointestinal: walls of digestive tract Urinary: walls of bladder & ureters Respiratory: airway passages Reproductive: uterus in females Ocular : eye (ciliary and iris muscle) Manipulating smooth muscle contraction and relaxation is key in management of many pathologies we discuss in this course! Differences btwn Skeletal and Smooth muscle Nervous Signals Hormonal (Autonomic) Smooth Stimulation Muscle Contraction Local Chemical Stretch of Muscle Conditions Local changes in chemical conditions and stretch of smooth muscle (vessel wall stress) is a big factor in blood vessels’ responsiveness to acute and chronic exercise. For example, nitric oxide (NO) signaling is enhanced with exercise and has multiple local mechanisms to increase smooth muscle relaxation, for blood vessel dilation  For example, nitric oxide (NO) signaling is enhanced with exercise and has multiple local mechanisms to increase smooth muscle relaxation, for blood vessel dilation Sports Med 2009 The Effect of Physical Exercise on Endothelial Func tion For example, nitric oxide (NO) signaling is enhanced with exercise and has multiple local mechanisms to increase smooth muscle relaxation, for blood vessel dilation  For example, nitric oxide (NO) signaling is enhanced with exercise and has multiple local mechanisms to increase smooth muscle relaxation, for blood vessel dilation Age-related arterial stiffness (shown here as a measured reduction in compliance) is improved with exercise training Symposium Review Aerobic exercise training and vascular function with ageing in healthy men and women 11 May 2019 https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP277764  Summary of Comparisons Between Muscle Types Skeletal Cardiac Smooth Synaptic transmission Pacemaker potentials Hormone-activated Mechanism of Neuromuscular Electrotonic receptors Electrical excitation transmission depolarization through coupling gap junctions Pacemaker potentials Action potential spikes, Electrical Action potential plateaus Graded activity of Action potential spikes plateaus membrane pot. changes muscle cell Slow waves Ca2+ sensor Troponin C Troponin C Calmodulin Ca2+ entry through voltage-gated L-type Ca2+ channel (DHP Ca2+ entry through L- Ca2+ channels Excitation- receptor) in T-tubule type Ca2+ channel (DHP 2+ Ca - and IP3-mediated contraction membrane coupling to receptor) triggers Ca2+- Ca2+ release from SR coupling Ca2+-release channel induced Ca2+ release Ca2+ entry through store- (ryanodine receptor) in SR from SR operated Ca2+ channels (ligand gated) Terminates Breakdown of ACh by Action potential Myosin light chain contraction Acetylcholinesterase repolarization phosphatase Twitch 200-400 ms 200 ms-sustained 20-200 ms (shortest) duration (intermediate) (longest) Balance between MLCK Regulation of Frequency and multifiber Regulation of calcium phosphorylation and  And norepinephrine! Also, if it is helpful, here’s a YouTube video where https://www.youtube.com/watch?v=nggYVmf7Qps skeletal and smooth muscle are compared/contrasted