Session 7 Notes: Neuromuscular – Chapter 11 p. 391-393, Chapter 12 p. 398-410

THE SOMATIC MOTOR DIVISION Control skeletal muscles. Have a single neuron originating in CNS and projects axon to skeletal

muscle. Always excitatory (unlike autonomic, which can be excitatory or inhibitory).

A SOMATIC MOTOR PATHWAY CONSISTS OF ONE NEURON Cell bodies of somatic motor neuron located in ventral horn or brain. Long axon that innervate

skeletal muscle target. Myelinated axons may be 1 meter+ Somatic motor neurons branch close to targets (at distal end). Each branch divides into a cluster of

enlarged axon terminals on the surface of skeletal muscle fiber. THUS, single motor neuron can control many muscle fibers.

Neuromuscular junction (synapse in somatic motor neuron/muscle fiber) has axon terminals, motor end plates on muscle membrane, and Schwann cell sheaths.

o Schwann cells secrete signal molecules for maintaining and forming neuromuscular junction.

Motor end plate has high concentrations of Ach receptors.

THE NEUROMUSCULAR JUNCTION CONTAINS NICOTINIC RECEPTORSo Action potential arrive at axon terminal, open voltage Ca2+,

calcium into cell, trigger Ach release. AcH binds to nicotinic receptors on skeletal muscle membrane.

o Fun fact: snake toxin binds to nAChR channels of skeletal muscle but not on neuron.

Nicotinic cholinergic receptors are chemically gated ion channels w/ 2 binding sites for Ach.

o Ach binds to receptor, channel opens, lets monovalent cations flow through.

o Net Na+ into muscle fiber, depolarization triggers action potential that causes muscle contraction.

o Ach acting on skeletal muscle’s motor end plate always excitatory and creates contraction. There’s no antagonistic innervation to relax muscles.

o Relaxation occurs when somatic motor neurons are inhibited in CNS, preventing Ach release???.

Another importance of exercise: If there’s less communication btwn motor neuron and muscle, skeletal muscles weaken! Use it or lose it!Ex: Myaesthenia gravis: disease of loss of Ach receptors. Muscles get weak b/c junction isn’t reinforced and communicated to.

Chapter 12: Muscles

Skeletal muscle: unique in that they can contract only w/ signal from somatic motor neuron. Can’t initiate own contraction, and contraction not influenced directly by hormones.

Smooth muscle : multiple levels of control, autonomic innervation. Some can contract w/out signals from CNS. Also affected by hormones.

All three: intracellular calcium signal, movement when myosin changes conformation w/ ATP.SKELETAL MUSCLEAntagonistic muscle groups: Ie. Flexor/extensor pairs. Necessary b/c a contracting muscle can pull a bone in one direction but can’t push it back. When one muscle contracts and shortens, the antagonistic muscle must relax and lengthen.

SKELETAL MUSCLES ARE COMPOSED OF MUSCLE FIBERSMuscle fiber: collection of muscle cells. Each fiber is sheathed in connective tissue.Satellite cells :stem cells committed to differentiate into muscle. Lie outside muscle fiber membrane.Fascicle: bundle of muscle fibers. Collagen, elastic fibers, nerves, blood vesicles are found between fascicles.

Muscle fiber anatomySarcolemma: muscle fiber membrane Sarcoplasm: cytoplasm Myofibril: In striated muscle; Highly organized bundle of contractile and elastic protein for contraction.Sarcoplasmic reticulum: modified ER that wraps around each myofibril like lace. Terminal cisternae: large regions w/ longitudinal tubules.

Stores Ca2+ in the SR membrane.

Ca2+ release from SR creates calcium signals.

T- tubules: associated w/ terminal cisternae. One t-tubule and 2 flanking terminal cisternae = triad. Membranes of t tubules are continuation of muscle fiber membrane. Thus lumen of t-tubules is continuous w/ extracellular fluid.Outside of clay (surface of muscle fiber membrane). It’s continuous w/ the hole you poked in the clay (membrane of t-tubule).

Cytosol btwn myofibrils have glycogen granules and mitochondria. Glycogen for energy. Mitochondria provide ATP.

MYOFIBRILS ARE MUSCLE FIBER CONTRACTILE STRUCTURES (muscle fibers consist of myofibrils)One muscle fiber has a thousand+ myofibrils that occupy intracellular volume. Little space for cytosol and organelles.

Myofibril have myosin, actin, tropomyosin, troponin, titin, nebulin Myosin: motor protein that creates movement. Thick filament.

o Heavy chain (motor domain) binds ATP and uses energy from ATP’s phosphate bond to create movement. Aka myosin ATPase. Also has binding site for actin.

o Light chain: smaller head. Actin: Thin filaments. One actin is a globular protein (G-actin).

o Multiple G actin molecules polymerize to form long chains and filaments (F-actin).o In skeletal muscle, two F-actin polymers twist like a double strand of beads.

Thick and thin filaments are connected by myosin crossbridges that span space btwn filaments. Each G-actin has a single myosin-binding site. Each myosin head has 1 actin binding site and 1 site for ATP. Crossbridges form when myosin heads bind to actin. Sarcomere: contractile unit.

o Z disk: filaments found between this. “zweischen” = between. Serve as attachment site for thin filaments.

o I band: lightest color. ONLY thin filaments. “isotropic” (region has light uniform color). Z disk runs through I band, each half of I band belongs to a different sarcomere. Shortens during contraction

o A band: Darkest region. Encompasses entire thick filament length. “anisotropic”. Protein fibers scatter light unevenly.

o H zone: center of A band. thick filaments only.o M line: “middle”. Like the Z disk for thin filaments. Divides A band in half. Represents proteins that

form attachment site for thick filaments. s

Titin: elastic molecule (biggest protein known!): Stretches from Z disk to M line. Stabilizes position of contractile filaments. Elasticity returns stretched muscle to resting length.Nebulin: inelastic giant protein that is alongside thin filaments. Attaches to Z disk. Helps align actin filaments of the sarcomere.

MUSCLE CONTRACTION CREATES FORCE1.Events at neuromuscular junction convert

acetylcholine signal from somatic motor neuron into electrical signal

2.Excitation-contraction (EC) coupling: process where muscle action potential initiate calcium signals that activate contraction-relaxation cycle.

3.Contraction-relaxation cycle: explained by sliding filament theory. 1 contraction-relaxation cycle is called a muscle twitch.

ACTIN AND MYOSIN SLIDE PAST EACH OTHER DURING CONTRACTION Z disk move closer together I band and H zone almost disappear. A band remains constant.

Notice: When you push on a wall, you create tension in muscles /out moving wall. Sliding filament theory explains how muscle can contract and create force w/out creating movement. Tension proportional to # of high force crossbridges btwn thick and thin filaments.

MYOSIN CROSSBRIDGES MOVE ACTIN FILAMENTS.

CALCIUM INITIATES CONTRACTION Resting skeletal muscle: tropomyosin is blocking myosin binding site on actin. When ca2+ binds to troponin, it moves tropomyosin so myosin can bind to actin. Relaxation requires Ca2+ in cytosol to decrease. Ca2+ unbind from troponin, and tropomyosin return to “off”

position, covering most of actin’s myosin binding sites. During this relaxation phase when actin and myosin are not bound to each other, the filaments of sarcomere slide back to original positions w/ aid of titin and elastic connective tissue in the muscle.

MYOSIN HEADS STEP ALONG ACTIN FILAMENTS Rigor state. Myosin is tightly bound to G-actin. No ATP present.

o Rigor state: State is brief in living muscle b/c muscle fiber has lots of ATP that binds quickly to myosin when ADP is released in step 4.

o After death, “rigor mortis”: muscles freeze b/c of immovable crossbridges. Persists a day after death until enzymes decay and break down muscle proteins.

1. ATP binds to myosin, myosin released from actin. 2. “relaxed state”: Myosin hydrolyzes ATP to ADP+Pi (which stay bound). Creates cocked position of 90 degr

and reattach to a new actin. Newly formed crossbridge is weak. Tropomyosin is partially blocking binding site on actin (see above pic of relaxed state). Most resting muscle fibers are in this state, cocked and prepared to contract, waiting for calcium signal.

3. Power stroke: begins after Ca2+ binds to troponin to uncover myosin binding site. Crossbridges transform into high-force bind as myosin releases Pi. Release of Pi lets myosin head sweivel toward M line, sliding to attached actin filament. Also called crossbridge tilting b/c myosin head tilt from 90 to 45angle.

4. Myosin releases ADP: at end of power stroke, myosin releases ADP. Myosin again tightly bound to actin in rigor state.