biophysics of muscle contraction ivan poliaček. types of muscles skeletal muscle - striated muscle...

BIOPHYSICS OF MUSCLE

CONTRACTIONIvan Poliaček

TYPES OF MUSCLES• Skeletal muscle

- striated muscle tissue existing under control of the somatic nervous system (voluntary control)

• Cardiac muscle - special striated muscle tissue of the heart working automatically and under the influence of autonomic nervous system (involuntarily)

• Smooth muscle - non-striated muscle tissue activated by autonomic nervous system, hormones, or simply stretching

Surrounds each bundle

cell

Surrounds

each cell

Fascia

Becomes the muscle

sheath which fuses

with the tendon

Bundlesof collagen

fibers

Deep structures of a sceletal muscle

Muscle fiber = muscle cell• The sarcolemma – the cell membrane (plasma membrane)

of a muscle cell

- conduct stimuli

- an outer coat (thin layer of polysaccharides with collagen fibrils) that fuses with a tendon fiber (they collect into bundles to form the muscle tendons)

• Sarcoplasm - cytoplasm with organelles• Myofibrils - cylindrical organelles

– contractive elements the actin and myosin filaments (the length a few μm)

– organized in repeated subunits along the length of the myofibril - sarcomeres

• Sarcoplasmic reticulum with T- tubules – internal

conductive system

Structure of

a musclecell

A microscopic photo and a scheme of

a maximum contraction of sarcomere is about 30%

Skeletal muscle

• attached to the bones for movement

• several types of fibers (speed, stamina, fatique, force, motor unit size, structure...)

• cells - long multi-nucleated cylinders - the length of muscle cell is a few mm (human sceletal muscle), the diameter is typically 100 - 150 μm

• cytoskeleton – supporting the cell shape

Summary 1

• What is basic and deep structure of skeleton muscle?• What is the sctructure of muscle cell (fiber)? How does

this cell look like?• What is the endomysium among the muscle cells for?• What organel is responsible for contraction – how is it

arranged?• What are contractille elements – molecules?• How is contraction performed?

What does drive the muscle?

What is making the muscle to contract?

Action potentialat the pre-synaptic membrane - activatesvoltage-gatedCa channels - Ca2+ influx - vesicles with neurotransmitter Acetylcholine (ACh) release acetylcholin into the synaptic cleft

Motor fibers (axons of motoneurons) within the motor nerves conduct action potentials to the neuro-muscular junction -

end-plate.

acetylcholine

nicotinicACh receptor

Acetylcholin binds with nicotinic receptors on postsynaptic membrane of muscle cell (motor end-plate) – activation of Na channels– depolarization = EPSP = end plate potential

• acetylcholine is eliminated by breaking down with the acetyl cholinesterase

Intracellular recordingfrom a muscle fiber

A nerve impulse reachingthe axon terminal releasesACh into the neuromuscular junction.ACh produces EPSP = end plate potential (EPP)in the membrane beneath the terminal (the subsynaptic = end-plate membrane) (A in the graph), but not fartheraway (B).When the EPP reachesthe threshold (about −50 mv), an action potential is generated that sweepsalong the fiber (A to B in the graph).

• If a single vesicle occasionally release ACh into the synaptic cleft the miniature EPSP (miniature end-plate potential) is produced – NO ACTION POTENTIAL follows

• Full EPSP full end-plate potential - EPP (due to synaptic action : AP – Ca2+ influx - many vesicles release) always reaches the firing level and produces action potential at the muscle cell.

• Action potential spreads along the sarcolemma and via T- tubules of the muscle cell depolarizes the terminal cisternae and the sarcoplasmatic reticulum.

Motor unit• Connective tissue separates

muscle cells - each one must be stimulated by a motoneuron

• Motor unit - all muscle cells innervated by the same motoneuron – they will contract at the same time

• Motor units vary in size - mostly mixture of motor units of different sizes

large motor units >100 cells (typically slow postural muscles)small motor units

about 10 cells (precise control fast acting muscles – those moving the eye)

Recruitment of motor units

Increasing level of central (moto-neuronal) activation – successive activation of higher threshold motor units

Summary 2• Where is the signal activating skeleton muscle coming from?

• Where is it transmitted to the muscle?

• What is the function of Ca++?

• What is the name for EPSP at the muscle cell?

• What receptors and what mediator are involved in synaptic transmission from the motoneuron to the muscle cell?

• What is the course of action potential at the muscle fiber?

• How far (where) the action potential at the muscle cell travel?

• How many muscle cells are supplied with single motoneuron?

• Can nearby muscle fibers be activated differently?

• When and how much are all muscle fibers activated?

The shape and some parameters of muscle fiber action potential

intracellular

extracellular

the rest

Extracellular recording of parasternal muscle EMG – 2 different motor units are present

200 μV

10 ms

The mechanism.

What happens on the way from action potential to the contraction of the

muscle?

The sarcoplasmic reticulum surrounds the myofibrils and holdsa reserve of the Ca2+ ions. A transverse T - tubules are the pathway for the action potential to signal the sarcoplasmic reticulum.

Action potential on T-tubules - depolarizes sarcoplasmic reticulum - activates voltage-gated Ca channels - Ca2+ released into intracellular space of muscle fiber

Ca2+ initiates muscle contraction

Muscle contraction is provided by interaction of ACTIN (thin) and MYOSIN (thick) fibers (filaments).

Tropomyosin covers binding spots of actin at a rest state.

Muscle contracts when myosin heads make a cross-bridges (bonds) with actin and the heads bend pulling the actin filament deeper among the myosin filaments.

the cycle : bind – bend – release1 stroke – 10-12 nm

As far as Ca2+ and ATP is present (around the Actin and Myosin) the cycle : binding, bending, releasing and straightening of myosin heads continue (contraction).

Ca2+ is constantly pumped (by a Ca pump) back into the sarcoplasmic reticulum (& extracellular space, tubules, cisternae).

In order to keep high Ca2+ concentration - further action potentials has to release it again and again.

Without Ca2+ tropomyosin returns back (conformation) over actin filament blocking its binding loci – stop contraction.

Crossbridge bindingScheme of chicken muscle myosin head. The movement is likely much more distributed including the movement at the actin-myosin interface.(Rayment et al. Science 261: 50-58, 1993)

Each myosin molecule contains two peptideheavy chains which are cleaved enzymaticallyto produce a myosin tail and two globularheads or crossbridges. The crossbridge heavy

chain has a tail region (shown in blue) aroundwhich two smaller peptides wrap. These peptidesare the light chains (yellow and red) which stabilize, and in some cases, regulate the myosin.

Myosin filament with myosin heads each 14.5 nm.

294 myosin molecules on the thick filament (588 ATP-ase binding spots).

Ca2+ binds with troponin, changes shape (conformation) of tropomyosin that exposes the actin

binding spots on actin filament.

The muscle contraction requires the ATP.

As the ATP is required to release the actin – myosin binding – without ATP : RIGOR MORTIS.

For the unbinding the myosin head from the actinand its “straightening”, the ATP is required.

Myosin hydrolyze ATP (lyse it into ADP and phosphate) gathering the energy

Summary 3• What is sarcoplasmic reticulum for?

• What happens when sarcoplasmic reticulum membrane is depolarized?

• What is the function of Ca++?

• What happens when the Ca++ is pumped back to the reticulum and other areas out of muscle cell intracellular space?

• How tropomyosin affect the muscle cell contraction?

• What is the role of ATP in muscle contraction?

• What happens when there is no ATP in the muscle cell?

• Why the sequence actin myosin connection – bending myosin heads (pulling the actin molecules) – release and stretch of myosin heads occur?

• For what exactly is the ATP energy used?

• Increased intracellular Ca2+ concentrations (Ca2+ released from sarcoplasmic reticulum and T – tubules) lasts longer than action potentials

• even longer lasts single muscle twitch

- no action potential from other than related motoneuron - SUMMATION is TEMPORAL at the level of Ca2+ release and twitches overlapping

Single muscle twitch

Single muscle twitch – unfused & fused tetanus

• A tetanic contraction - motor unit stimulated by a high frequencyof action potentials from its motoneuron

• The time between stimuli is shorter than single twitch durations – no time to relax - superposition of muscle twitches and (temporal) summation of contraction

• The strength of contractions increases- it is added to the previous twitch

Incomplete (unfused)tetanus

Complete (fused) tetanus

The opposite acting muscle to the agonist is the antagonist (e.g. flexing the elbow biceps brachii - agonist, the triceps brachii - antagonist)

An antagonist is never totally relaxed

- control and damping of movement by maintaining tone against the agonist (eccentric movement)

Summary 4• What is the duration of the action potential, increased Ca++

intracellular concentration, and single muscle twitch?

• What type of summation works for muscle contraction?

• How many motoneurons can stimulate the particular muscle cell?

• Compare the frequencies of activation of a muscle cell during unfused and fused tetanus?

• How is maximum contraction of the muscle cell achieved?

• How are working oppositely connected muscles?

Summary of muscle

contraction

• Short rest

• The time for thinking and organizing infos.

MUSCLE PROPERTIES• Elasticity or recoil

- muscles have elastic elements which cause them to recoil to their original size.

• Stretchability or extensibility - muscles can also stretch and extend to a longer-than-resting length

• Excitability and responsiveness - muscle tissue can be stimulated by electrical,

physical, or chemical means• Contractility – transformation of chemical energy

into the mechanical work - movement

- the response of muscle tissue to stimulation is contraction, or shortening

muscles can only pull, they cannot push

Smooth muscle• Visceral (smooth) muscle

- in the body's internal organs and blood vessels- no striations- layers in the mucous membranes of the respiratory and digestive systems, bands in the walls of blood vessels, and sphincter muscles.

• Smooth muscle fibers - a fusiform shape - a spindle-like shape (wide in the middle and tapers at both ends) - 20-500 μm in length.

• The ratio of actin to myosin is ~ 6 : 1 in skeletal muscle, 4 : 1 in cardiac muscle and ~ 16.5 : 1 in smooth muscle.

• Greater elasticity and ability to stretch and still maintain contractility than striated muscle.

Intestine smooth muscle

Smooth muscle contraction• Contraction - sliding of myosin and actin

filaments - hormones, neurotransmitters, drugs, etc.

• Single unit smooth muscle tissue is connected into a syncytium - the autonomic nervous system innervates a single cell within a sheet or bundle - the actionpotentialpropagatesby gap junctions to neighboring cells (all contract together).

• Smooth muscle may contract spontaneously- it is myogenic (via ion channel dynamics or pacemaker cells - interstitial cells of Cajal inthe gastrointestinal tract).

Smooth muscle contractionMultiunit smooth muscle tissues - individual cells are innervated by the autonomic nervous system (fine control and gradual responses, much like in skeletal muscle) - the trachea, the elastic arteries, the iris of the eye).

No troponin, but instead calmodulin is regulatory protein in smooth muscle, also tropomyosin doesn't serve the regulatoryfunction as in striated muscle.Contraction is initiated by a Ca-regulated phosphorylation of myosin, rather than a Ca-activatedtroponin system.

Smooth muscle thinfilaments – mainlyactin, tropomyosin, and caldesmon.

Summary 5• What is elasticity, stretchability, excitability, and contractiliry?

• What are main differences between skeletal and smooth muscles?

• What does it mean syncytium?

• What does it mean myogenic activity?

• What is the molecule the Ca++ interact with in the smooth muscle vell instead of troponin of skeleton muscle cell?

• How is contraction of multiunit smooth muscle cell initiated?

Heart muscle • Cardiac muscle - much shorter cells than skeletal muscle- cardiac muscle cells connect to

one another - gap junctions -

intercalated discs - electrochemical

impulse can pass to all connected cells - syncytium (the cells work as a unit)

Faint striations - similar, but not identical, arrangement of myofilaments in cardiac and skeletal muscleMany cardiac muscle cells are myogenic – activation arises in the heart

not from the nervous system - heart natural rhythm

A scheme of intercalated discs of cardiac muscle

gap junctions create cytoplasmic bridges

cytosol

connexin proteines

intercellular space

cell membrane

• In cardiac myocytes, influx of Na trigger calcium-induced calcium release - Ca2+ influx through voltage-gated calcium channels on the sarcolemma leading to the release of Ca2+ from the sarcoplasmic reticulum

and its relation to the ECG waveform

Long-lasting action potential - long refractory period- no temporal summation - no tetanic contraction

Relation of electrical and mechanical characteristics of heart action

Spreading of electrical(action potential) activity from the sinoatrial node to the tissue of heart atria & atrioventricular node and theninto the ventricular heart tissue with the recording of the related ECGwaveform.

Summary 6• What is function of intercalated discs?

• How are cardio-myocytes activated?

• What is calcium induced calcium release?

• What is the consequence of it?

• How much longer is cardio-myocyte action potential than neuron action potential?

A comparison of the propertiesof skeletal, cardiac, and visceral muscle

 Property SkeletalMuscle

 CardiacMuscle

 SmoothMuscle

 Striations?  Yes Yes  No

 Relative Speed of Contraction

Fast   Intermediate  Slow

 Voluntary Control? Yes  No No

 MembraneRefractory Period

 Short  Long  

 Nuclei per Cell  Many  Single  Single

 Control of Contraction

 Nerves

 Beats spontaneously

but modulated by nerves

 NervesHormones

Stretch

 Cells Connected byIntercalated Discs or

Gap Junctions? No  Yes  Yes