ASEN 5016 Lecture 13: Skeletal Muscle Response to Space Flight (guest lecturer, Andrea Hanson)

1. Differentiate between different types of muscle

2. Describe major components of muscle structure and function

3. Distinguish between slow twitch vs. fast twitch fibers

4. Describe the effects due to space flight on skeletal muscle and ways to counteract the undesirable responses

5. Discuss applied research on skeletal muscle atrophy

1. Types of muscle.

Smooth - involuntary muscle of the stomach, intestine, and blood vessels

- or visceral -- not under direct (voluntary) nervous control.

- In walls of alimentary tract, blood vessels, arrector pili

- Slow and sustained response

Skeletal - voluntary, striated muscles attached to bones

- Mostly under direct (voluntary) nervous control.

Cardiac - involuntary muscle of the heart wall.

- Also striated, but specialized and confined to the heart

2a. Skeletal Muscle Physiology

Skeletal muscle makes up ~40% of body mass

Each muscle has a bone attachment point

Contractions are coordinated by the brain and carried out through a complex system of axons, motor neurons and neurotransmitters

The postural or ‘anti-gravity’ muscles maintain strength by working against the gravity gradient

-located from the lumbar spinal area to the feet (ex: gluteal muscles, quadriceps, gastrocnemius, soleus)

2b. Skeletal Muscle Structure

Muscle consists of fascicles

Each fascicle contains muscle fiber (myocyte) bundles

Each myocyte contains 100’s – 1000’s of Myofibrils

Each Myofibril has ~3000 Actin & ~1500 Myosin filaments

Myosin filament is ~ 1.6 microns long

Actin filament is ~1 micron long

An individual myosin molecule is ~490 kD

Titin component – thought to be basis of muscle stiffness, bears passive load in muscle

Nebulin – passive component, also thought to add to stiffness, by binding actin monomers together

Satellite Cells – stem cells that have the ability to differentiate into myoblasts and form new muscle fibers

-essential to repair after injury

-molecular manipulation may form basis for gene therapy of muscular and genetic disorders in the future

3. Contraction Events

Two primary contractions: Isotonic (constant tension) and Isometric (constant length)

ATP needed for three steps in the contraction relaxation process

-energy for the power stroke of the cross bridge

-binding to myosin permits detachment from actin, and allows next cycle

- transporting Ca++ back into the SR

Motor neuron from spinal cord innervates muscle

Action potential opens channel in bilipid membrane

Acetylcholine (AChe) is released and binds to channel

Channel of ~0.65 nm allows positive ions in (primarily Na⁺, plus K⁺ and Ca⁺⁺)

Na⁺ influx reduces negative potential inside cell

This depolarizes the membrane and allows a large Ca⁺⁺ influx

Ca⁺⁺ causes conformational change of actin filament sub-components, uncovers binding sight between actin and myosin

ATP (produced by mitochondria) is "waiting" for binding sight

As a result… ATP is cleaved à energy and ADP

ATP energy causes myosin head to "snap" and moves actin

Release of ADP causes myosin head to "snap back" to next site

Series causes a ratcheting motion resulting in muscle contraction

Pumps then activate to remove Ca⁺⁺ and relax contraction

AChe esterase breaks AChe down into acetate ions and choline

Pyruvate a byproduct of anaerobic glycolysis, lactic acid is a byproduct

Choline is recycled, acetate is a toxic byproduct

Common misconception that lactic acid build-up leads to muscle soreness

Acid build-up will cause burning sensation, but micro damage to contractile proteins and swelling causes soreness commonly referred to as ‘Delayed Onset Muscle Soreness’

Demo link – http://www.blackwellpublishing.com/matthews/myosin.html

Fatigue occurs when AChe is used up (first step in Ca⁺⁺ influx)

Atrophy occurs through disuse or denervation

4. Slow Twitch vs. Fast Twitch Fibers

Fast – larger fibers, greater strength of contraction, easily fatigued, lots of innervation (quick response), lots of enzymes for breaking down glycogen into energy, less extensive blood supply (use glycogen rather than oxygen), fewer mitochondria (which are mainly an oxidative energy process)

e.g. eyes and fingers

Slow – smaller fibers, innervated by smaller nerves (usually not as quick of a response needed), more extensive oxygen use (more blood vessels), a lot of mitochondria, contains myoglobin in muscle cells (binds oxygen to provide instantaneous supply), longer to fatigue, brownish red color

e.g. back muscles

"Marathoners" tend to have increased ratio of slow twitch fibers

"Sprinters", conversely, have more fast twitch fibers

The number of muscle fibers remains more or less constant, but training can:

· increase size of individual fibers (hypertrophy)

· increase level of vascularization (# of capillaries)

· increase amount of mitochondria (ATP factories)

· alter proportion of fast to slow twitch muscles, and vise-versa

5. Effects due to space flight

Disuse results in opposite consequences to hypertrophy – muscles atrophy

Muscle atrophy is "selective", based on function

Muscles with anti-g function atrophy most (typically slow fibers)

Experiments have shown that slow fibers decrease in CSA and number of occurrence, increased expression of fast type fibers, no net change in fast fiber CSA

- Not sure why this occurs

- Supply and demand theory

Even though the max force potential is reduced in space, the ability to sustain force is apparently maintained (no change in fatigue)

soleus (anti-g, postural) reduced by up to 50%

gastrocnemius – jumping (H-reflex) not as impacted

Post-mission muscle soreness is a reported problem. Long mission duration crew members (~3 months or longer) undergo at minimum a 45 day rehabilitation program.

Russian studies pertaining to muscle volume, fiber size, atonia and contractility

Potential role of afferent signals (dry immersion vs. bed rest)

Stiffness of gastrocnemius muscle (largest, most prominent muscle of the calf of the leg, the action of which extends the foot and bends the knee) shown to decrease by ~50% during dry immersion (weightless analog) almost immediately with little change in flexors

Bed rest, on the other hand, shown to be ~600x slower response time

System theorized to recognize that weight simply altered from foot to back, but still present, therefore, changes driven by weight-bearing afferentation

(afferent sensor - Carrying inward to a central organ or section, as nerves that conduct impulses from the periphery of the body to the brain or spinal cord)

Countermeasures

Exercise, Penguin Suit, pharmaceutics, nutrition, electrical stimulation

6. Applied Research on Muscle Atrophy

Hindlimb suspension: unloads the hind-limbs only, simulates cephalid fluid shift

Myostatin is a suppressor of skeletal muscle proliferation, may be a significant treatment for muscle atrophy in the near future

Strength tests, such as HEFT and electrophysiology, can help determine efficacy of treatments

Western blot analysis can reveal how proteins in the atrophy pathway interact to cause muscle loss

STS-118 carried an experiment testing a myostatin agonist, producing very positive results that may lead to a muscle atrophy countermeasure

Overall response is very complex, but bottom line is that muscles normally used to maintain posture are most affected in space

Interesting abstract regarding atmospheric effects on training – http://www.go2altitude.com/data/Melissa1997.html

Article on Muscle Physiology and Spaceflight effects courtesy of ASGSB-http://asgsb.org/factsheets/muscle.html