1. Muscles Striated Cardiac Smooth Excitability and contractibility

2. animations http://www.dnatube.com/video/4875/Physiology-of-muscle- contraction-and-relaxation http://www.dnatube.com/video/1306/Role-of-myosin- crossbridge-in-the-contraction-of-muscle http://www.dnatube.com/video/1952/Sliding-filament-causes- contraction-of-muscle http://www.dnatube.com/video/4154/Cellular-mechanism-of- muscular-contraction

3. Striated muscle – sarcomere

4. Striated muscle – sliding of contractile elements

5. Striated muscle – motor unit

6. Striated muscle – neuromuscular junction

7. Striated muscle – myography, tetanus Muscle contraction Twitch Summation Superposition Tetanus Smooth - multiple summation Undulating – multiple superposition

8. Muscle strength Muscle strength depends on the number of motor units recruited Strength depends only on cross-sectional area 20 – 100 N per sq.cm Muscle cells cannot divide. Thickening is formed by duplication of myofibrils. Muscle strenght is influenced –genetically –hormonally – testosterone, anabolics

9. Muscle strength – tension/length curve, isometric and isotonic contraction

10. 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 Anaerobic Glycolysis –Enzymatic breakdown of the glucose 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 oxygen Oxidative metabolism – the final source of energy –95% of all energy used by the muscle

11. 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, spasm, cramp 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)

12. Muscle fatigue Acute (recovery - within 24 hours) and chronic (may be followed by a complete exhaustion) Decrease force of muscle contraction Fatigue –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 –decreasing amounts of muscle glycogen –Accumulation of lactate – lower pH, increase of K +, stimulation of the free nervous endings – pain, edemas –exhaustion of ATP

13. Striated muscle – twitch = types of muscles

14. TYPE I - SLOW TWITCH Tonic muscles (darker: red) - Leg muscles TYPE II - (IIa & IIx) FAST TWITCH Tetanic muscles (paler: white) - Pectoral muscles longer contraction times (100-110 msec)shorter contraction times (50 msec) contain myoglobin (red)no myoglobin (white) continuous use muscles - prolonged performance for endurance performance ( marathoners) one time use muscles - brief performances for power & speed (sprinters) marathoner: 80% type I & 20% type IIsprinter: 20% type I & 80% type II best in long slow sustained contractionsbest in rapid (short) contractions not easily fatiguedeasily fatigued more capillary beds, greater VO 2 max less capillary beds smaller in sizelarger in size lower glycogen contenthigher glycogen content poor anaerobic glycolysis * predominantly anaerobic glycolysis easily converts glycogen to lactate wo O 2 * predominant aerobic enzymes & metabolismsome aerobic capacity higher fat contentlower fat content more mitochondria - Beta Oxidation highfewer mitochondria- Beta Oxidation low poorly formed sarcoplasmic reticulumwell formed sacroplasmic reticulum slower release of Ca = slower contractionsquick release of Ca = rapid contractions tropinin has lower affinity for Catroponin - higher affinity for Ca

15. Muscle pain During exercise Ischemic, hypoxic, accumulation of metabolites, pH Fast in, fast out Difficult to localize (muscle, bone, tendom, joint) Referred pain (viscero somatic hyperalgesia) After exercise Dull ache when moving or being palpated Begins in 1-3 days and lasts for one week Maximal isometric strength is not impaired Does not correlate with muscle edema, plasma CK, inflammation markers

16. Drugs that modify neuromuscular junction Botulinum toxin prevents acetylcholine release – spasms (torticolis) Methacholine, carbachol and nicotine – the same effect as Ach – not destroyed by acetylcholinesterase – long action – Ophtalmology (glaucoma) Muscle relaxants – general anesthesia – muscle relaxation. Curare (D-tubocurarine) blocks acetylcholine receptors w/o depol Succinylcholine is a depolarizing blocker Anticholinesterase drugs, neostigmine and physostigmine – reversible inactivation of acetylcholinesterase – accumulaiton of Ach – myasthenia gravis Organophosphate – chemical weapons – irreversible inactivation of acetylcholinesterase – cramps, respiratory distress, sweating and convulsions. Dandrolen blocks Ca realease from SR – malignant hypetermia

17. Smooth muscle - structure actin and myosin no troponin, calmodulin instead Dense bodies – analog of Z-lines – attachment of actin filaments Actin – long filaments, 15 times as myosin Contraction 30 times slower than that of sceletal muscle constant power during contraction (isotonic line longer, since some contractile units have optimal overlapping of A&M at one length of the muscle and others at other length)

18. Types of smooth muscles Multiunite –discrete smooth muscle –single nerve ending –The ciliary muscle of the eye (parasympathetic control) –The piloerector muscles (sympathetic control) Single-unit (visceral) –Hundreds to millions contract together – syncythial –gap junction – ions can flow freely –gut, bile ducts, ureters, uterus, vessels

19. 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

20. Mechanism of contraction Beginning of contraction 4 Ca 2+ bind with regulatory protein calmodulin Complex Ca-calmodulin activates enzyme myosin 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 phosphorylation of myosin head Enzyme myosin phosphatase splits the phosphate from the regulatory light chain

21. Smooth muscle - contraction

22. 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

23. 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

24. 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

25. StriatedSmooth SarcomereYesNo NucleiManyOne Sarcoplasmatic ret.LargeSmall T-tubulesYesno (caveoli) A:M ration2:115:1 Length of ActinShortLong Actin fixingZ-lineDense bodies Conduction speedHighLow Contraction speedHighLow Resting potential-90mV-60 mV, fluctuate ExpandibilitySmalllarge (10x)

26. StriatedSmooth Regulatory proteinTroponinCalmodulin, myosinkinase TwitchFast & shortSlow & long End of contraction↓ Ca Spontaneous ↓ Ca Myosinphosphatase Consuption of ATPHighLow ConnectionSynapseVaricosities ControlMotoneuronepacemakers Autonomic NS humorální Mechanical FatigueYesAlmost not

27. striatedsmooth NeuromediatorAcetylcholine (nor)Adrenalin Source of CaSarcoplasm retExtracellular space