PROF STEIN LECTURE 8-MUSCULOSKELETAL SYSTEM+MOVEMENT

WHAT ARE THE 3 TYPES OF MOVEMENT?

• AMEBOID

• CILIARY MOVEMENT

• MUSCULAR MOVEMENT

WHAT ARE THE ENDO AND EXOSKELETONS DIAGRAM?

• MUSCLE CAN SHORTEN + PULL

• LOOK AT DIAGRAMS

WHAT ARE THE 3 TYPES OF MUSCLE?

• SMOOTH

• CARDIAC (STRIATED)

• SKELETAL (STRIATED)

  • FAST TWITCH

  • SLOW TWITCH

WHAT IS THE DIFFERENCE BETWEEN SLOW AND FAST TWITCH IN SKELETAL MUSCLE?

SLOW TWITCH-RED, GOOD FOR ENDURANCE, MORE MYOGLOBIN+STORED OXYGEN

FAST TWITCH-WHITE, GOOD FOR SPRINTS, LEANS ON GLYCOLYSIS/AEROBIC RESPIRATION

WHAT IS HOMEOSTASIS AT THE MOLECULAR LEVEL; CHOs?

LOOK AT DIAGRAM

WHAT ARE THE 3 FATES FOR GLUCOSE AGAIN?

1) METABOLIZE FOR ATP (IF ATP IS HIGH THEN)

2) STORE AS GLYCOGEN (IF GLYCOGEN IS HIGH THEN)

3)STORE AS FAT

THE “DECISION” TO SWITCH BETWEEN 1, 2, AND 3 IS MADE BY BUILDUP OF PRODUCTS AND SENSITIVITY OF ENZYMES

WHAT IS A MUSCLE FIBER?

MUSCLE CELL, ONE MEMBRANE SURROUNDS A VERY LARGE CELL

WHAT IS THE MYOFIBRIL, (PART OF SKELETAL MUSCLE) AND WHAT IS IT MADE OF?

• CONTRACTILE ELEMENT INSIDE OF CELLS; SPANS THE LENGTH OF MUSCLE

• IT IS MADE OF REPEATED SARCOMERES

WHAT IS A SARCOMERE?

• CONTRACTILE UNIT INSIDE OF MYOFIBRIL; CHAIN OF SARCOMERES MAKE UP A MYOFIBRIL, AS EACH SARCOMERE SHORTENS BY 1 UM IN UNISON, CHAIN OF SARCOMERES (MYOFIBRIL) SHORTENS BY CENTIMETERS

WHAT IS THE ANATOMY OF SKELETAL MUSCLE?

LOOK AT DIAGRAM (IT CONSISTS OF MUSCLE FIBER, MYOFIBRILS, AND SARCOMERES)

WHAT ARE THE BASIS OF MUSCLE SHORTENING?

• SLIDING FILIMANTS

• ACTIN = THIN FILIMANT

• MYOSIN = THICK FILIMANT

• CROSSBRIDGES

WHAT ARE Z LINES, AND WHAT IS THE DIFFERENCE BETWEEN EXTENDED AND CONTRACTED MUSCLES?

• Z LINES BIND SARCOMERES

• Z LINE CONNECTS 2 ADJACENT SARCOMERE

• SARCOMERES ARE “STITCHED” TOGETHER AT Z LINES TO FORM WHOLE LENGTH OF MYOFIBRIL

WHAT IS THE MATH EXAMPLE FOR AN EXAMPLE OF MUSCLE?

LOOK AT DIAGRAM

SO HOW DOES A SARCOMERE SHORTEN BY 0.5 UM?

• EACH MYOSSIN HEAD UNDERGOES A CONFORMATIONAL CHANGE THAT EQUATES TO A FEW NM CHANGE OF LENGTH. EACH OF THESE “MOLECULAR MOTORS” SHORTENS THE SARCOMERE A LITTLE BIT AT A TIME TO EQUAL UM

WHAT IS A “MOLECULAR MOTOR” FOR MOVEMENT?

• CONFORMATIONAL CHANGE IN PROTEIN (MYOSIN HEAD)

WHAT ARE THE 2 STEPS TO EXPOSING MYOSIN BINDING SITES?

A) TROPOMYOSIN AND TROPONIN WORK TOGETHER TO BLOCK THE MYOSIN BINDING SITES ON ACTIN

B) WHEN A CALCIUM ION BINDS TO TROPONIN, THE TROPONIN-TROPOMYOSIN COMPLEX MOVES, EXPOSING MYOSIN BINDING SITES

WHAT ARE THE 5 STEPS OF HOW ACTION POTENTIALS TRIGGER MUSCLE CONTRACTION?

1) ACTION POTENTIAL ARRIVES; ACETYLCHOLINE (ACH) IS RELEASED

2) ACH BINDS TO ACH RECEPTORS ON THE MUSCLE CELL, TRIGGERING DEPOLARIZATION THAT LEADS TO ACTION POTENTIAL

30 ACTION POTENTIALS PROPAGATE ACROSS MUSCLE CELL’S PLASMA MEMBRANE AND INTO INTERIOR OF CELL VIA T TUBULES

4) PROTEINS IN T TUBULES OPEN CA2+ CHANNELS IN SARCOPLASMIC RETICULUM

5) CA2+ IS RELEASED FROM SARCOPLASMIC RETICULUM. SARCOMERES CONTRACT WHEN TROPONIN AND TROPOMYOSIN MOVE IN RESPONSE TO CA2+ AND EXPOSE ACTIN BINDING SITES IN THE THIN FILAMENTS

HOW MUCH ENERGY DOES IT TAKE TO MOVE 1 KG OF ANIMAL ONE METER?

• COST OF TRANSPORT (COT) IS LESS FOR LARGER ANIMALS (J/KG/M)

• LOWEST COT FOR SWIMMING, THEN FLYING, THEN RUNNING

LOOK AT DIAGRAM

WHAT ARE THE TWO MAIN TOPICS OF SPORTS PHYSIOLOGY?

1) EXERCISE PHYSIOLOGY

2) IMPROVEMENTS THROUGH TRAINING

WHAT ARE THE MUSCLE FIBER TYPES AND WHAT ARE THEY USED FOR?

• SLOW TWITCH (ENDURANCE)

• FAST TWITCH A (INTERMEDIATE)

• FAST TWITCH B (SPRINTS)

MAKE-UP CALF MUSCLE…A COMPARISON

marathon runner-90% slow twitch

sprinter-25% slow twitch

WHAT DOES THE SLOW TWITCH, FAST TWITCH A, FAST TWITCH B COMPARISON DIAGRAM STATE?

LOOK AT DIAGRAM

WHAT ALLOWS FOR IDENTIFICATION OF SLOW AND FAST-TWITCH MUSCLE FIBERS?

• DIFFERENTIAL STAIN FOR MYOSIN

• POWER ATHLETE ON LEFT (MORE FAST TWITCH)

• ENDURANCE ATHLETE ON RIGHT (MORE SLOW TWITCH)

• I-SLOW TWITCH

• II-FAST TWITCH

WHAT ARE ENERGY SYSTEMS DESCRIBED AS?

• SOURCE OF ATP FOR CROSS BRIDGE FORMATION

• RATE OF DELIVERY OF ATP LIMITS NUMBER OF CROSSBRIDGE CYCLES PER SECOND

WHAT ARE THE 3 TYPES OF ENERGY SYSTEMS?

• PHOSPHAGEN SYSTEM (10 SECONDS)

• GLYCOLYTIC SYSTEM (1-2 MINUTES)

• OXIDATIVE (AEROBIC) (INDEFINITE)

WHAT IS THE PHOSPHAGEN SYSTEM?

• STORED ATP+PHOSPHOCREATINE

• 4 MOLES ATP/MIN

WHAT IS THE GLYCOLYTIC SYSTEM?

• INEFFICIENT BUT FAST

• BUILDUP OF LACTIC ACID

• 2 MOLES ATP/MIN

WHAT IS THE OXIDATIVE SYSTEM?

• VERY EFFICIENT BUT SLOW

• 1 MOLE ATP/MIN

WHAT IS THE CAPACITY OF SYSTEM VS. EXERCISE DURATION?

LOOK AT DIAGRAM

WHAT IS FIBER TYPE RECRUITMENT ORDER?

• AS YOU INCREASE THE EFFORT YOU RECRUIT MORE NUMBERS OF FIBERS BUT WHAT ABOUT FIBER TYPE?

• LOW INTENSITY (WALK; SLOW JOG)

  • SLOW TWITCH

• MEDIUM INTENSITY (FAST JOG; RUN)

  • SLOW TWITCH PLUS FAST TWITCH A

• HIGH INTENSITY (RUN; SPRINT)

  • SLOW TWITCH PLUS FAST TWITCH A PLUS FAST TWITCH B

WHAT IS THE FIBER TYPE RECRUITMENT ORDER?

• IS REFLECTED IN THE TYPE OF FUEL THE BODY USES %FAT VS %CARB

WHAT IS THE LOW INTENSITY FIBER TYPE RECRUITMENT ORDER?

• (WALK; SLOW JOG)

• SLOW TWITCH (60% FAT, 40% CARB)-ST FIBERS PRIMARILY USE FAT AT A SLOW RATE

WHAT IS HIGH INTENSITY FIBER RECRUITMENT ORDER?

• (RUN; SPRINT)

• SLOW TWITCH PLUS FAST TWITCH A PLUS FAST TWITCH B

• 5% FAT, 95% CARB

• DUE TO SHIFT IN ST FIBERS FROM FAT TO CARB AND MOST SIGNIFICANTLY FROM THE MASSIVE AMOUNTS OF CARBS UTILIZED IN FAST TWITCH A AND B FIBERS

FATIQUE: WHAT IS ENERGY DEPLETION?

• PHOSPHOCREATINE (SHORT, HARD EFFORTS)

• GLYCOGEN DEPLETION (LONGER EFFORTS)

FATIQUE: WHAT IS BUILDUP OF METABOLIC BYPRODUCTS?

• CURRENT RESEARCH DOES NOT SUPPORT LACTIC ACID DIRECTLY WEAKENING MUSCLE CONTRACTION (AN OLD STORY)

• ELECTROLYTE CHANGES (INTRACELLULAR OR EXTRACELLULAR)

  • INCREASE IN EXTRACELLULAR K+

  • DEPOLARIZATION OF VM OF MUSCLE CELLS

  • LESS RELEASE OF CA++ FROM SARCOPLASMIC RETICULUM

FATIQUE: WHAT IS THE NERVOUS SYSTEM?

PHYSIOLOGICAL (SPINAL CORD REFLEXES) AND PSYCOLOGICAL

WHAT IS ENDURANCE TRAINING AND WHAT ARE ITS MAIN POINTS (9 POINTS)?

• V_O2=CO*(O_2A- O_2V)

• STRONGER HEART (INCREASE SV)

• MORE BLOOD VOLUME (INCREASE SV)

• INCREASED VASCULARIZATION (LOWER TPR—> INCREASE SV) AND MORE CAPILLARIES DECREASES DISTANCE FROM BLOOD TO MITOCHONDRIA (DECREASE O_2V)

• MORE HEMOGLOBIN (INCREASE O_2A)

• MORE MITOCHONDRIA (DECREASE O_2V)

• MORE OXIDATIVE ENZYMES (DECREASE O_2V)

• INCREASED MYOGLOBIN (A BUFFER TO STAY OXIDATIVE WHILE BLOOD DELIVERY CATCHES UP TO DEMAND)

• PSYCHOLOGICAL FACTORS (BECOME COMFORTABLE WITH/EMBRACE PAIN + DISCOMFORT)

WHAT IS ACTN3 AND WHAT IS ITS DIAGRAM?

• A GENETIC INFLUENCE ON MUSCLE FUNCTION AND ATHLETIC PERFORMANCE

• LOOK AT DIAGRAM

WHAT DOES AN ACTN KNOCKOUT MOUSE PROVIDE?

• IT PROVIDES MECHANISTIC INSIGHTS INTO THE ASSOCIATION BETWEEN ALPHA-ACTININ-3 DEFICIENCY AND HUMAN ATHLETIC PERFORMANCE

• A common nonsense polymorphism (R577X) in the ACTN3 gene results in complete deficiency of the fast skeletal muscle fiber protein a-actinin-3 in an estimated one billion humans worldwide. The XX null genotype is under-represented in elite sprint athletes, associated with reduced muscle strength and sprint performance in non-athletes, and is over-represented in endurance athletes, suggesting that a-actinin-3 deficiency increases muscle endurance at the cost of power generation. Here we report that muscle from Actn3 knockout
  mice displays reduced force generation, consistent with results from human association studies. Detailed analysis of knockout mouse muscle reveals reduced fast fiber diameter, increased activity of multiple enzymes in the aerobic metabolic pathway, altered contractile properties, and enhanced recovery from fatigue, suggesting a shift in the properties of fast fibers towards those characteristic of slow fibers. These findings provide the first mechanistic explanation for the reported associations between R577X and human athletic performance and muscle function.