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.
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!
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
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”.
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.
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 LiverBack 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.
All skeletal myofibers are not equal 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!
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?)
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?
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
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!
Axons can deliver an AP to smooth muscle tissues by innervate several different smooth muscle cells via structures called varicosities!