Myosin Contracts Skeletal Muscle Jonathan P. Davis, Ph.D. Assistant Professor Office/Lab Phone Department of Physiology and Cell Biology, The Ohio State University, 400 Hamilton Hall

Muscle Skeletal CardiacSmooth

Thick Filament or Myosin Regulation In these cases: Myosin needs to be “activated” before it can interact with actin or move cargo

Actin Binding Proteins Like Tropomyosin Regulate Myosin Thin Filament Regulation Weak Electrostatic Myosin Binding Sites Strong Hydrophobic Myosin Binding Sites “Blocked State” “Closed State” “Open or M State” Tropomyosin “Rocks and Rolls”

Structure of Skeletal (striated) Muscle Comprised of fibers (cells) Each fiber contains many myofibrils in parallel Each myofibril contains many sarcomeres in series Striations due to characteristic banding pattern of sarcomere Electron micrograph of Skeletal Muscle Fiber

Sarcomere Composed of Overlapping Thin and Thick Filaments The Sarcomere

CROSS-BRIDGES PROJECT FROM THICK TO THIN FILAMENTS Z Line Cross-bridge H-Zone

The Thin Filament Is Composed Primarily of Actin but Also Contains Tropomyosin and the Troponin Complex 1)Troponin C – Binds Calcium 2)Troponin I – Inhibits Cross-Bridge Binding 3)Troponin T – Binds Tropomyosin Complex The Troponin Complex Contains Three Proteins

The transverse tubules bring action potentials into the interior of the skeletal muscle fibers, so that the wave of depolarization passes close to the sarcoplasmic reticulum, stimulating the release of calcium ions. The extensive meshwork of sarcoplasmic reticulum assures that when it releases calcium ions they can readily diffuse to all of the troponin sites. T-tubules and the Sarcoplasmic Reticulum

Cell Membrane T -Tubule Sarcoplasmic Reticulum ACTION POTENTIAL CAUSES RELEASE OF CALCIUM FROM SR Calcium SR Ca 2+ ATPase Ryanodine Receptor Dihydropyridine Receptor Calsequestrin

Mechanism of Skeletal Muscle Activation by Ca 2+ 1) “off” state- absence of Ca 2+ Tm blocks myosin binding 2) “on” state- Ca 2+ binds to TnC Tm moves toward center of actin Myosin binding sites exposed Muscle contracts **Tm can occupy 2 positions: “off” and “on” state

Time [Ca 2+ ] Plasma Membrane T-Tubule Sarcoplasmic Reticulum Regulation of Striated Muscle Contraction 1) Action Potential2) Calcium Transient Calcium 3) Calcium Binds Troponin C Actin Tropomyosin Troponin Complex - Ca 2+ + Ca 2+ Myosin Binding Site 4) Myosin Power Stroke *** ATP Driven Power Stroke & Detachment*** Actin Myosin Actin Myosin 5) Force Production –Ca 2+ Relaxed +Ca 2+ Contracted **SR Ca 2+ ATPase**

Greater the force against which shortening occurs, the slower the velocity of shortening Muscles exhibit > 200-fold variation in maximum velocity of shortening. Why? Maximum velocity of shortening Reflects speed of cross-bridge cycling Is  actomyosin ATPase activity Is determined by differences in the myosin molecule ISOTONIC AND ISOMETRIC CONTRACTIONS A – 100% Maximal Force B – 75% Maximal Force C – 50% Maximal Force D – 25% Maximal Force A B C D A B C D Maximal Velocity (V MAX ) Force Muscle Shortening Time =  L/  T

RELATIONSHIP OF ELECTRICAL TO MECHANICAL EVENT IN SKELETAL MUSCLE CONTRACTION Calcium Transient (Shortening or Force Generation)

FORCE DEVELOPMENT IN AN ISOMETRIC CONTRACTION AS A FUNCTION OF STIMULUS FREQUENCY

Isometric contraction at each length In the body Skeletal muscle operates at plateau of length-force relation Cardiac muscle operates on the ascending limb of length-force relation ACTIVE, PASSIVE AND TOTAL FORCE VERSUS MUSCLE LENGTH

MECHANISM OF LENGTH-FORCE RELATIONSHIP IN MUSCLE

CLASSIFICATION OF SKELETAL MUSCLE FIBERS Classification system of muscle fibers is based on: Rate of ATP utilization and capacity to re-synthesize ATP Physiological implications of these parameters Muscles are heterogeneous with different proportions of fiber types depending on function

RELATIONSHIP OF MOTOR UNITS TO INNERVATED MUSCLE FIBERS AND RECRUITMENT Slow-oxidative Fast-oxidative Fast- glycolytic

LEVER RELATIONSHIP OF MUSCLE TO BONE AFFECTS FORCE DEVELOPMENT AND VELOCITY

EFFECTS OF FATIGUE ON SKELETAL MUSCLE FIBERS TYPES What Could be Happening? 1)Conduction Failure 2)Energy Metabolism Biproducts A) Lactic Acid B) Phosphate and ADP

III.Geometry of Muscle a. Direction fibers run in the muscle b. Lever system