MUSCLE PHYSIOLOGY Physiology Unit 2
MUSCLE PHYSIOLOGY
Physiology Unit 2
Excita2on-‐Contrac2on Coupling
• Sequence of events from the genera2on of an AP across the sarcolemma to cross-‐bridge cycling inside of the myofiber
• Sarcolemma is an excitable membrane – Genera2ng an AP – Propaga2ng an AP – Similar mechanisms as neurons
Motor Neurons
• Soma2c motor neurons innervate skeletal muscle • Soma located in the brain stem or spinal cord • Largest diameter neurons • Myelinated
� High velocity AP • Upon reaching muscle, axon divides into many branches • Each branch forming a single junc2on with a muscle fiber
Neuromuscular Junc2on Membrane Excita2on
• Axon terminal meets with the motor end plate of the sarcolemma
• Axon terminal contain vesicles that store ACh • ACh is released and binds to N-‐ACh receptors on the
motor end plate (ligand gated Na+ channels) • Generates an end-‐plate poten2al (EPP)
Ac2on Poten2al in the Sarcolemma
Ac2on Poten2al to Contrac2on • AP lasts 1-‐2 ms • Completed before any
mechanical ac2vity begins • Mechanical ac2vity
(contrac2on) may last >100 ms
• Electrical ac2vity (ac2on poten2al) does not act on contrac2le proteins
• Produces a state of increased cytolsolic [Ca2+] – Res2ng [Ca2+] = 0.1 mMol/L – AXer AP [Ca2+] = 1 mMol/L
Skeletal Muscle
• Muscle cells – Striated – Mul2nucleated – Voluntary
• Organiza2on – Myofiber • Myofibril – Myofilament
Sarcomere
• Func2onal unit of skeletal muscle
• Composed of 3 filaments – Thick filament
• Myosin
– Thin filament • Ac2n • Troponin • Tropomyosin
– Elas2c filament • Ti2n
Thick and Thin Filaments
Ac2va2on by Ca2+
• Tropomyosin covers the myosin binding sites on ac2n
• Troponin has 3 sub-‐units 1. Troponin I
• inhibitory 2. Troponin T
• Tropomyosin binding
3. Troponin C • Calcium binding
• Increase in cytosolic [Ca2+] ac2vates cross-‐bridge cycling
Troponin
Sarcoplasmic Re2culum • Lateral sacs store Ca2+
– Ca2+ bound to calsequestrin • T-‐tubules lie between lateral sacs
– Membrane is capable of propaga2ng an AP
• T-‐tubules and lateral sacs are connected by foot processes (junc2onal feet)
– T-‐tubule has DHP receptors • DHP receptors are normally
voltage gated Ca2+ channels • In skeletal muscle t-‐tubules, acts
as a voltage sensor
– SR has ryanodine receptors • Intracellular Ca2+ channels
Sliding Filament Theory of Contrac2on
• Cross bridges form between the thick and thin filaments
• Thin filaments slide across the thick filaments – Thin filaments will move
closer together – Distance between Z lines
decreases – I band and H bands shorten
during contrac2on – A band stays the same
Cross Bridge Cycling
1. Acachment of the cross-‐bridge to a thin filament 2. Movement of the cross-‐bridge, pulling on the thin
filament – Each cross-‐bridge moves independently of all other
cross-‐bridges
3. Detachment of cross-‐bridge from the thin filament 4. Energizing the cross-‐bridge so it can again acach to
a thin filament and repeat the cycle
Cross-‐Bridge Cycling
Cross Bridge Cycling Steps • Fiber is res2ng, access to myosin binding site on ac2n is
blocked and myosin heads are not acached. • Myosin head is ac2vated; myosin + ATP = myosin x ADP + pi • Cross bridge formed by myosin head binding to ac2n • Power stroke causes filaments to slide • New ATP molecule binds to myosin heads to release from
ac2n • Myosin is ac2vated by myosin ATPase enzyme splifng new
ATP • Cycling con2nues • This results in asynchronous pulling ac2on
Skeletal Muscle Contrac2on
ATP in Muscle Metabolism Uses of ATP in Muscle
Contrac=on
• Ac2va2on of myosin – High-‐energy myosin
• Release of myosin head from ac2n molecule
• Ac2ve transport of Ca2+ into SR from the sarcoplasm
Muscle Contrac=on Requires A Lot of ATP!
• No ATP “storage” • 3 pathways for regenera2on – Phospagen system – Glycolysis – Aerobic respira2on
Energy ATP + H20 à ADP + pi + H+ +
Sources of ATP
1. Phosphagen System 2. Glycolysis 3. Oxida2ve phosphoryla2on
Phosphagen System
• Crea2ne Kinase – Present at 3x higher concentra2on in skeletal muscle
– Produced by liver – CrP + ADP + H+ -‐-‐-‐-‐> Cr + ATP
• Adenylate Kinase – ADP + ADP -‐-‐-‐-‐ > ATP + AMP
Aerobic Respira2on
• Primary source of ATP produc2on for muscle during rest or light exercise
• Fuel u2liza2on by skeletal muscle – facy acids – muscle glycogen – blood borne glucose
Anaerobic Mechanisms • Oxygen consump2on – Exercising muscle can consume more ATP than can be produced by aerobic respira2on
– Muscle cells will u2lize available glucose and glycogen reserves
– Glycolysis will then produce ATP to keep up with the demand of the ac2ve muscle • Lac2c acid accumulates
– Oxygen Debt • The amount of oxygen consumed to get the muscle cells and plasma back to normal condi2ons – Glucose levels – Glycogen reserves – Conver2ng lac2c acid back to pyruvic acid
Smooth Muscle • single cells, no stria2ons • circular layer
arrangement • no sarcomeres or
troponin • ac2n:myosin ra2o = 13:1 • u2lizes Ca2+/calmodulin
mechanism • graded depolariza2ons • single unit vs mul2-‐unit • autonomic innerva2on
Smooth Muscle