Muscle Structure, EC Coupling & Work (Ex Phys)

• Homeostasis

  The tendency toward a relatively stable equilibrium between interdependent elements, especially as maintained by physiological processes
• The body is constantly combating entropy (state of disorder) with internal control and balance. Variables are kept in balance for a whole lifetime because of regulation of enzymatic properties.
• Homeostasis

  1. Receptor (sensor) monitors the environment and responds to stimuli

  2. Control center determines set point and receives input from receptor, determines appropriate response

  3. Effector receives output from control center and provides the means to respond, response acts to reduce or enhance the stimulus (feedback)

  
• Components of a Biological Control System

  • Receptor (sensor)
  • Control center
  • Effector
• Positive feedback


  Feedback that adds onto the original stimulus
• Negative feedback


  Feedback that opposes the stimulus and brings the variable back to a set point
• Positive feedback


  Amplifies the effect of the stimulus until an end point is reached. Happens when end point needs to happen quickly.
• Failure of any component of a control system results in a disturbance of homeostasis

  
  

  i.e., Type 1 Diabetes; damage to beta cells in pancreas -> insulin no longer released into blood -> glucose is no longer being uptook from the blood by the liver or muscle -> hyperglycemia occurs

  • this represents failure of the effector - the message is being sent but not received
• Exercise disrupts homeostasis by changing pH, O2, CO2, and temperature
• Steady state


  A state in which a particular variable is oscillating about a point, but energy must be continuously added to maintain this variable constant

  • this is an acute response to exercise; demand on the body = the body's response to those demands
  • the variable will STILL be oscillating during a steady state!
• What happens to the body's core temperature during exercise?

  Gradual increase in body temp first 40 minutes, then steady state plateau 40-60 minutes of exercise
• Food + O2 → ATP + CO2 + H2O + Heat
• Some variables naturally oscillate around a mean value, such as arterial pressure (mean arterial pressure remains constant while arterial pressure oscillates over time)
• Gain of a control system 


  Degree to which a system maintains homeostasis (the efficiency of it).
• Gain = CORRECTION/error


  i.e., mean BP increased 100 to 150 via a drug, after 5 minutes BP returned to 110. The gain is [(110-150)/(110-100)] = [-40/10] = -4
• A system with large gain is more capable of maintaining homeostasis than a system with low gain!


  i.e., pulmonary and CV systems have large gains
• Renal pressure/volume control is tightly regulated because error is zero, (#/0) = infinity (so the gain is infinity)
• Feed-forward system is the anticipatory effect one intermediate exerts on another further along the pathway; allowing the system to anticipate changes. 


  i.e. thinking about an upcoming run, heart rate increases before starting run
• Why is 1-2 lb weight loss per week recommended?

  Because we have to allow the body to change in that set point of where BW is being maintained, otherwise weight is gained back very quickly!
• Three fundamental processes of SKM:


  • Ca++ cycling
  • Crossbridge cycling
  • Cellular respiration
• Thick Filament

  about 300 myosin molecules make up a thick filament
• Myosin Molecule


  2 heavy Chains ( Myosin Heavy Chain [MHC]) make up the tail, 4 Light Chains (Myosin Light Chain [MLC]) primarily in neck region molecule
• Myosin Binding Protein-C (cardiac specific isoform)-> regulatory


  Acts as a tether to the myosin heads, to limit mobility, it decreases the # of cross-bridges formed, which impacts force generation. When phosphorylated (β-adrenergic stimulus)- accelerates cross-bridge formation, enhancing force and promoting relaxation
• Actin has two forms:

  1. actin-globular form (messy)
  2. F-actin-filament form (beads on string)
• Tropomyosin-> regulatory protein!


  Turn the contractile apparatus on/off, In the groove of F-actin molecules, Supports rigidity of the thin filament, Blocks the myosin binding site on actin, Each tropomyosin binds one troponin complex
• Troponin-> regulatory


  Turn the contractile apparatus on/off,

  Subunits:

  • Troponin-T - binds to Tropomyosin
  • Troponin-I - facilitates the inhibition of myosin binding to actin (covers binding sites more)
  • Troponin-C - calcium binds to it and pulls tropomyosin out of the way
• Nebulin


  Highly elastic, regulates thin filament length
• Titin


  Functions as a molecular spring and is highly responsible for passive force development

  • coils and when muscle stretches, Titin uncoils but wants to recoil just as much
• Obscurin


  Important for the organization of the sarcomere, and assembly
• Myomesin


  Links antiparallel myosin fibers and titin filaments, potential signal of sarcomere damage

  • connects myosin to one another
• M-Protein

  Provides stability to myomesin
• MuRF-1


  Upregulated with atrophy (casting, immobilization, denervation, etc)
• Duchenne Muscle Dystrophy (DMD)- most common, 1 in 3500 male children, severe muscle wasting and most patients are wheelchair bound by the age of 12 and many die of respiratory failure in their 30-40's

  • DMD is irregular, abnormal, or lacking dystrophin protein
• Stages of an action potential

  • Resting potential (-70 mV): because potassium is high inside cell and sodium is low, compared to EC Matrix
  • Threshold (allows opening up of sodium voltage gated channels, allowing influx of sodium into cell)
  • Depolarization: Sodium floods cell, making voltage become +
  • Repolarization: sodium channels close and potassium channels open, lots of potassium leaves the cell and voltage goes back down below resting
  • Resting potential
  • Hyperpolarization: membrane potential more negative than default rest voltage, will eventually go back to resting in milliseconds
• T- tubules

  Have a Dihydropyridine (DHP) receptors -type of sensor that is voltage dependent - senses voltage change from action potential and change shape, opening calcium channels in SR and allowing calcium to flood the cell (initiating TnC binding to have troponin move tropomyosin...)
• Ryanodine Receptor


  The terminal cisterna of the SR have these, they are a Ca2+ channel on the SR that is physically connected to the DHP receptor
• ¼ of the total of SR calcium is released into the myoplasm in a single twitch contraction of muscle.
• T-tubules in Cardiac Muscle have a voltage sensitive L-Type Calcium Channel, which allows EC Ca2+ to enter cardiomyocyte. This is not enough calcium to trigger contraction!
• Coupling in Cardiac muscle:

  • CICR is calcium induced calcium release, happens when:

  • t-tubules have voltage sensitive L-type Calcium channel that senses the voltage change, allowing extracellular calcium to enter the cardiomyocite.
  • Then, Ca2+ binds to Ryanodine Receptor on sarcoplasmic reticulum
• Muscle relaxation is dependent on the SERCA, which is:

  Sarcoplasmic endoplasmic reticulum calcium ATPase pump, activated by high Ca2+ in the myoplasm and is ATP dependent because it has to work against the concentration gradient