MUSCLE II Skeletal muscle Muscle force, muscle work, muscle fatigue Smooth muscle Heart muscle

Skeletal muscle – types of contraction Isometric contraction Muscle contracts against a force transducer Muscle does not shorten during contraction Isotonic contraction Muscle shortens against a fixed load Muscle shortens, tension remains constant –Myographic curve on kymograph

Types of myographic curves - tetanus Muscle contraction – twitch Summation Superposition Tetanus Smooth - multiple summation Undulating – multiple superposition

Relation of muscle length to force of contraction Resulting force of contraction is a sum of: Active tension during contraction Passive tension (resting tension) (sarcolemma, vessels, nerves)

Relation of velocity of contraction to load maximal – when muscle contracts against no load zero - when muscle contracts against maximal load

Muscle force Muscle force depends on the number of motor unit Motor unit – all muscle fibers innervated by a single motoneuron (from 2-3 up to several hundred muscle fibers) The total strength of the muscles in the human body is 250,000 N (Newtons). –1 Newton (N) = 1 kg.m/s 2 Muscle force is influenced –genetically –hormonally – testosterone, anabolics

Muscle hypertrophy Enlargement of a total mass of muscle Increased number of myofibrils Increased amount of mitochondrial enzymes - up to 120% Increased amount of ATP and kreatinphosphate - up to % Increased amount of glycogen - up to 150% Increased amount fat deposits - up to %

Types of skeletal muscle fibers Fast fibers – white Longer fibers for great strength of contraction Extensive sarcoplasmic reticulum for rapid release of Ca 2+ Large amounts of glycolytic enzymes for rapid release of energy Less excessive blood supply (oxidative metabolism is of secondary importance) Fewer mitochondria Adapted for rapid, powerful contraction (jumping, sprints) Every muscle is composed of a mixture of fast and slow muscle fibers

Types of skeletal muscle fibers Slow fibers - red Smaller fibers Innervated by smaller nerve fibers More capillaries – to supply extra amount of oxygenu Increased numbers of mitochondrias (high level of oxidative metabolism) Large amount of myoglobin (Fe containing protein, similar to hemoglobin - red color) Adapted for prolonged, continuous muscle activity (antigravity muscle, long-distance races) Every muscle is composed of a mixture of fast and slow muscle fibers

Muscle work Muscle work = the effect of the muscle force on a certain path (A = F. s) (J) Dynamic (during isotonic contraction, movement) More extensive blood supply Intensive circulation during relaxation Static (changes of muscle tension without the shortening of the muscle) Lesser blood supply Limited circulation - accumulation of metabolites – development of muscle fatigue

Muscle fatigue Acute (recovery - within 24 hours) and chronic (may be followed by a complete exhaustion) Decrease force of muscle contraction Fatigue is localized in the neuromuscular junction –Accumulation of extracellular K + may lead to a disturbance in depolarization, reduction of the amplitude of the action potential and conduction velocity Muscle fatigue is increasing parallel to decreasing amounts of muscle glycogen Accumulation of lactate – lower pH, increase of K +, stimulation of the free nervous endings – pain, edemas Contracture – long-lasting muscle contraction – without action potentials, exhaustion of ATP

Orbeli phenomenon Effect of epinephrine – a transitory increase of muscle force contraction appearance of the fatigue is postponed by the sympathetic stimulation Fatigue appears before the energetic reserves of the organism are exhausted Fatigue is a physiological protective phenomenon preventing the damage to the organism

Sources of energy for muscle contraction ATP – maintains contraction for 1 to 2 seconds phosphocreatine – 5 times as great as ATP, sufficient for 7-8 s contraction Glycogen –Enzymatic breakdown of the glycogen to pyruvate and lactate liberates energy that is used to convert ADP to ATP, glycolysis can sustain contraction for about 1 min Twofold importance of glycolysis –Reactions occurs in the absence of oxygen (muscle contraction can be sustained for a short time when oxygen is not available) –The rate of formation of ATP is 2.5 times as rapid as ATP formation with oxygene –Accumulation of many end-products Oxidative metabolism – the final source of energy –95% of all energy used by the muscle

Function of ATP ATP is necessary for Muscle contraction – detachment of the head of myosin from the actin Function of Na + /K + pump Function of Ca ++ pump Physiological depletion of sources of ATP (reversible) – contracture Irreversible loss of all ATP – rigor mortis –Lack of energy for the separation of cross-bridges –Rigor is faster after muscle fatigue and exhaustion –Muscles remain in rigor until muscle proteins are destroyed by autolysis (15-25 hours)

Smooth muscle - structure Contains actin and myosin, it does not contain troponin Dense bodies – analog of Z-lines – attachment of actin filaments Actin – long filaments 15 times as many actin as myosin Contraction of smooth muscle is about 30 times slower than contraction of skeletal muscle Great ability to shorten with full force of contraction Some contractile units of smooth muscle have optimal overlapping of their actin and myosin filaments at one length of the muscle and others at other length

Types of smooth muscles Single-unit (visceral) –Hundreds to millions of muscle fibers contract together as a single unit – syncithial smooth muscle –The cell membranes are joined by gap junction – through which ions can flow freely from one cell to the next cell –Visceral organs of GIT, gut, bile ducts, ureters, uterus, vessels Multiunite –Is composed of discrete smooth muscle fibers –Each fiber operates independently of others –Is innervated by a single nerve ending –The ciliary muscle of the eye (parasympathetic control) –The piloerector muscles (sympathetic control)

Contraction of smooth muscle Initiating event in smooth muscle contraction is an increase in intracelullar Ca 2+ ions cause by: –Nerve stimulation –Stretch of the fiber –Hormonal stimulation –Changes in the chemical environment of the fiber Strength of contraction depends on extracellular Ca 2+ Removal of Ca 2+ ions is achieved by calcium pump, calcium pump is much slower in comparison with a pump of skeletal muscle – longer contraction

Mechanism of contraction Beginning of contraction 4 Ca 2+ bind with regulatory protein calmodulin Complex Ca-calmodulin activates enzyme miosin kinase (a phosphorylating enzyme) Light chain of of each myosin head (regulatory chain) become phosphorylated, the head has the capability of binding with the actin filaments Cessation of contraction: When the concentration of Ca 2+ falls bellow a critical level, all processes automatically reverse except for the fphosphorilation of myosin head Enzyme myosin phosphatase splits the phosphate from the regulatory light chain

Smooth muscle - contraction

Smooth muscle – membrane potential Smooth muscle has more voltage-gated calcium channels and very few voltage-gated sodium channels than skeletal m. Importance of Ca 2+ ions in generating smooth muscle action potential – phase plateau of AP, contraction Slow wave Resting potential –50 to –60 mV Spontaneous slow wave (some smooth muscle is self- excitatory) Slow wave can initiate action potentials (-35 mV) The more AP, the stronger contraction

Contraction without action potentials In multiunite smooth muscle, Ca 2+ ions can flow into the cell through the ligand-gated Ca 2+ channel –ligand – acetylcholine, norepinephrine Action potentials most often do not develop Membrane potential do not reach a critical level for generating action potential because the Na + pump pumps sodium ions out of the cell

Regulation of smooth muscle Smooth muscle are regulated by autonomic nerves Nerve fibers do not make direct contact with smooth muscle fibers – they formed so-called diffuse junction Terminal axons have multiple varicosities, containing vesicules In the multiunite type of smooth cells, the contact junctions are similar to the end plate of skeletal muscle

Heart muscle - structure The cardiac muscle is striated as skeletal muscle Has typical myofibrils that contain actin and myosin filaments Heart muscle is a syncitium -- gap junctions connection Intercalated discs – membrane with low resistance AP travel from one cardiac muscle cell to to another

Heart muscle - action potential Resting potential –80 to –95 mV Amplitude 105 mV Phase of plateau Duration 200 – 300 ms

Regulation of cardiac muscle Sympathetic nervous system Norepinephrine binds to adrenergic receptors and activates Ca 2+ channel (Ca 2+ flows into the cell – increases positivity inside) Increases frequency Increases strength of contraction Increases conductance Increases excitability Parasympathetic nervous system Acetylcholine binds to muscarine cholinergic receptors and activates K + channel (K + flow from the cell – increases negativity inside) Hyperpolarization makes excitable tissue much less excitable Slowing transmission Decrease of frequency

Skeletal m.Smooth muscle Sarcomereyesno Nucleusa lot ofone Sarkopl. reticulum well developedmoderately T-tubulesyesno (caveoli) Content of actomyosin higherlower Ratio A:M2:115:1 Actin filamentsshortlong Plasticitylowhigh (10x) Conductancefasterslower Velocity of contraction rapidslower Resting potential-80 to –90 mV -50 to –60 mV unstable

Skeletal m.Smooth muscle Excitation- contraction coupling Ca- TN-C TN-I Ca-calmodulin myozin kinase Cessation of contraction Ca decrease spontaneously Ca decrease myozin phosphatase Energy from ATPhighlow Autonom. contraction noyes pacemaker Controlmotoneuronsautonomic NS humoral mechanical Fatigueyespractically not