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Mechanism of Myofiber Contraction: Depolarization and Calcium Release

This article explores how depolarization of the muscle cell membrane leads to calcium release, which subsequently triggers myofiber contraction. It also discusses the factors that limit depolarization and contraction, the role of conditioning and exercise, and the physiology of smooth and cardiac muscle.

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Mechanism of Myofiber Contraction: Depolarization and Calcium Release

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  1. How Does Depolarization Cause Myofiber Contraction?Oct 25 and 27 What are membrane potentials? How does the action potential reach a myofiber? Why does a depolarized myofiber contract? What limits depolarization and contraction? What is fatigue? How are myofiber functions specialized? How does conditioning and exercise effect myofibers? Review of smooth muscle and cardiac muscle physiology.

  2. We make a muscle cell contract by depolarizing it, causing calcium release. How do we polarize a membrane creating membrane voltage and what is depolarization? What are the relative Na+, K+ and Ca++ concentrations on the inside/outside of the plasma membrane? • Pumps maintain this difference at ATP cost! • Why does this create a voltage (membrane potential)? • Ways to depolarize the membrane: 1) Ligand-gated channels: Acetylcholine 2) Voltage-gated channels: Na+ or Ca++ 3) Gap junctions: cardiac and some SMC 4) Stretch-gated channels or damage Arrival of an action potential at a motor end plate is critical for skeletal myofiber coupling of depolarization and contraction!

  3. The arrival of an action potential at a neuromuscular junction is the critical event for muscle depolarization/contraction by a somatic motor neuron. • 1) Arrival of AP depolarizes end of axon (synaptic knob). • 2) Depolarization of knob causes voltage gated calcium channels to open on knob. • 3) Ca++ enters and causes vesicular exocytosis acetylcholine (ACH) released into synaptic cleft. • 4) ACH diffuses 50-100 nm to nicotinic receptors for ACH on sarcolemma (motor end plate). • 5) ACH-gated Na+ channels open (also open to K+) and end plate potential (EPP) created on target cell (slight depolarization) • 6) If the axon is stimulated several times, several additive EPPs create enough local depolarization to open neighboring voltage gated Na+-channels. • 7) New action potential created and Ca++ enters myofiber

  4. How does a membrane depolarization cause calcium to enter a muscle cell? • 1) Changing membrane potential (voltage) • 2) T-tubules carry depolarization deep within the myofiber to sarcoplasmic reticulum! • 3) SR Ca++channels open for a short period • 4) Calcium enters cytosol from the sarcoplasmic reticulum and t-tubules • 5) Ca++ binds troponin and tropomyosin removed! • 6) Actin/Myosin contact each other! • 7) Myosin-ATPase: “Power stroke” is possible when ATP is hydrolyzed to ADP and Pi! • 8) New ATP makes next wrachet-cycle possible with the • “recovery stroke”.

  5. What limits the duration of contraction? • 1) ACH is rapidly degraded by acetycholinesterase, thus limiting duration of ligand channel opening. • 2) Voltage gated Na+ channels stay open for only a few microseconds and then close and stay closed until the membrane can hyperpolarize again. • 3) Na+/K+-ATPase rapidly repolarizes membrane nd the Ca++-ATPase pumps Ca++ back into S.R. • 4) ATP supply must be sufficient for power stroke • 5) ATP supply must be sufficient for the myosin head to release actin and move to next actin subunit (recovery stroke) • Test Question: Memorize steps, structures and chemicals in Figures 11.7, 11.8, 11.9, and 11.10. • Be able to interpret figure 11.11 in regards to why one sarcomere has optimal, sub-optimal and failing force generation at different length-orientations.

  6. What causes muscle fatigue? 1) What is VO2-Max? Why is VO2-Max so important? Oxygen supply=ATP production 2) Major fuels: Glycolysis in cytosol and fatty acid oxidation in mitochondria, both create NADH 3) Mitochondria use NADH to make ATP with oxygen required as electron acceptor 4) Mitochondria #1 ATP production site if O2 present 5) What happens when ATP demand surpasses the supply of oxygen required by mitochondria for ATP production? Lactic acid metabolism starts in cytosol: Pyruvate Lactate Blood and LiverBack to glucose Lactate Dehydrogenase: special enzyme associated with myofiber injury/death! Oxygen Debt during exercise: The difference between the baseline oxygen consumption rate and the elevated rate during exercise.

  7. All skeletal myofibers are not equal!Some are specialized for aerobic activity and some for anaerobic activity! Two Fiber Types! Slow Oxidative: myoglobin and mitochondria rich Excellent ability to generate ATP Slow onset to ATP production peak (15-20 min) Demand large amounts of oxygen Generate “long lasting” twitch (up to 100 msec) You want these for running a marathon! Fast Glycolytic: glycogen and glycolytic enzyme rich Excellent ability to make fast ATP via glycolysis Fatigue quickly and have fewER mitochondria Generate “quick” twitches (of about 7.5 msec), unable to sustain twitch due to limited ability to make large amounts of ATP once glycogen reserves have been used up. You want FastGlycolytic to run a 100 yard dash!

  8. What factors determine muscular strength and our level of muscle conditioning? • Number of myofibers does not change! • Muscle/myofiber size: (actin/myosin content?) • Fascicle arrangement: (strength or length?) • Recruitment of motor units: (# myofibers?) • Temporal summation: (# of APs?) • Length-tension arrangement at start: (optimal?)

  9. How does exercise influence metabolism in muscle cells? • Conditioning of metabolic activities in cells: What changes occur? • How long till fatty acid metabolism? Impact on weight-loss programs? • Resistance(anaerobic) vs. Endurance (aerobic): • What happens during deconditioning?

  10. Review: Basically cardiac muscle is similar to, but not identical to skeletal muscle! • There is no tetany in the heart! • Size of cells relatively compact! • Depolarization is due to autorhythmic changes • No motor endplates! Small cells! One nuclei! • Nervous input only MODIFY contraction. • Calcium still removes troponin! • Oh Yes! Cardiac Myocytes have No Motor Endplates! Autorhythmicity

  11. Smooth muscle is a different kind of muscle! • Calcium activates calmodulin • Calmodulin-Ca activates myosin-light chain kinase! • Phosphorylated myosin contracts! • Actin/myosin loosely organized! • Multiunit SMC: vs Singleunit SMC One axons-distinct endings vs Varicosities off one axon • Varicosities, Gap Junctions, Synapse/MotorEPs • Effects of stretch and plasticity!

  12. Axons can deliver an AP to smooth muscle tissues by innervate several different smooth muscle cells via structures called varicosities!

  13. Smooth Muscle cells contain actin and myosin, but are quite different from skeletal and cardiac myocytes. 1) Where do we find smooth muscle under involuntary control? 2) Smooth Muscle usually comes in flat sheets or tubes with cells that may or may not be connected by gap junctions. 3) The gut and artery have both circular and longitudinally arranged sheets of smooth muscle to complement each others function. Function of circular fibers Function of longitudinal fibers 4) In smooth muscle cells the actin and myosin are not organized into sarcomeres, but more loosely attached to the plasma membrane and sarcoplasm (no striations) 5) Smooth Muscle can generate force that is sustained for a longer time and uses less ATP (its cells typically have fewer mitochondria and rely more on glycolysis) 6) Smooth muscle is stimulated by the autonomic NS at a classic synapse (Multi-unit) or via a series of varicosities from a single axon (Single-Unit) where gap junctions carry depolarization to neighboring cells.

  14. Smooth muscle cells are found in blood vessels, glands, guts,and other places. SMCs contract using calcium entry/calmodulin binding as a signal to activate myosin light chain kinase (MLCK). MLCK phosphorylates myosin letting it bind actin and contract.

  15. Once the myosin in smooth muscle is phosphorylated it binds actin and the cell contracts, contraction ends when Ca++ leaves the cell and MLC-phosphatase removes the phosphate from MYOSIN…leading to SMC relaxation

  16. Smooth Muscle Applications: Asthma: excess constriction of airways Solution: promote dilation (reduce SMC contraction) High Blood Pressure: Excess contraction of blood vessel Solution: vasodilator drugs Low Blood Pressure: Not enough SMC tone in blood vessels. Solution: vasoconstrict blood vessels to push blood back to heart Peristaltic Waves in intestine: propel chyme, often the contractions are not strong enough (constipation)…what is the solution? Hypermotile Intestine (Diarrhea): Solution is to reduce intestinal SCM contractile force Hyperactive Bladder: improve receptive relaxation

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