BIOFISIKA OTOT BIOFISIKA OTOT (Biophysics of Muscle) (Biophysics of Muscle) H Aqsa Sjuhada H Aqsa Sjuhada Building DR-G, Room G-101 Building DR-G, Room G-101 Graduate School of Medicine Graduate School of Medicine Dept of Physiology, Airlangga Dept of Physiology, Airlangga University University Tel. (031) 71200 999 Tel. (031) 71200 999 E-mail. [email protected]E-mail. [email protected]
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BIOFISIKA OTOTBIOFISIKA OTOT(Biophysics of Muscle)(Biophysics of Muscle)
H Aqsa SjuhadaH Aqsa Sjuhada Building DR-G, Room G-101Building DR-G, Room G-101Graduate School of MedicineGraduate School of Medicine
Dept of Physiology, Airlangga UniversityDept of Physiology, Airlangga UniversityTel. (031) 71200 999Tel. (031) 71200 999
• Classification and characteristicsClassification and characteristics
• General functionGeneral function
• Cellular mechanism of contractionCellular mechanism of contraction
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Without muscles our bones could not move, Without muscles our bones could not move, our lungs could not breathe, and our heart our lungs could not breathe, and our heart
would not beat - we would die! would not beat - we would die!
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GENERAL GENERAL CHARACTERISTICSCHARACTERISTICS
- Chemically and electrically excitableChemically and electrically excitable- Mechanically contraction, activated Mechanically contraction, activated
by action potentialby action potential- Divided into Divided into skeletalskeletal, , smoothsmooth and and
cardiaccardiac muscle muscle
• NEWBORNNEWBORN : 25% BW: 25% BW
• YOUNG ADULT YOUNG ADULT : 40% BW: 40% BW
• MIDDLE AGEDMIDDLE AGED : 30% BW: 30% BW
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SKELETAL MUSCLESKELETAL MUSCLE- Makes up the great mass of the somatic Makes up the great mass of the somatic
musculaturemusculature- Has well-performed cross striationsHas well-performed cross striations- Doesn’t contract without nervous Doesn’t contract without nervous
stimulation, under voluntary controlstimulation, under voluntary controlCARDIAC MUSCLECARDIAC MUSCLE- Has cross striationsHas cross striations- Contracts rhythmically, involuntary controlContracts rhythmically, involuntary controlSMOOTH MUSCLESMOOTH MUSCLE- Lacks cross striationsLacks cross striations- Contain pacemakersContain pacemakers- Builds the viscera organsBuilds the viscera organs
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SIFAT UMUM OTOTSIFAT UMUM OTOT
- Peka rangsangPeka rangsang
- Elastic / bila ditarik kembali Elastic / bila ditarik kembali memendek spt semulamemendek spt semula
single cell, single cell, multinucleated,multinucleated,long, cylindrical, long, cylindrical, surrounded by cell surrounded by cell membrane membrane (sarcolemma)(sarcolemma)
Epimysium :Epimysium :Pembungkus kumpulan fasciculusPembungkus kumpulan fasciculus
Fascia :Fascia :Pembungkus terluarPembungkus terluar
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MYOFIBRIL DAN MYOFIBRIL DAN MYOFILAMENMYOFILAMEN
Myofibril :Myofibril :Organelle yang terdiri dari banyak myofilamenOrganelle yang terdiri dari banyak myofilamen
Myofilamen terdiri dariMyofilamen terdiri dari1.1. ActinActin2.2. MyosinMyosin
Actin terdiri dari :Actin terdiri dari :1.1. ActinActin2.2. TropomyosinTropomyosin3.3. Troponin : C , I , TTroponin : C , I , T
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TROPONIN ITROPONIN I ::
Inhibit the interaction between myosin Inhibit the interaction between myosin and myosinand myosin
TROPONIN TTROPONIN T ::
Ikatan dengan tropomyosinIkatan dengan tropomyosin
Troponin CTroponin C ::
Binding sites for calciumBinding sites for calcium
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SLIDING PHENOMENASLIDING PHENOMENA
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Besar kontraksi dipengaruhi oleh :Besar kontraksi dipengaruhi oleh :
1.1. Initial lengthInitial lengthMakin panjang initial length, makin Makin panjang initial length, makin besar kontraksinya (dalam batas besar kontraksinya (dalam batas fisiologis)fisiologis)
2.2. SuhuSuhuMakin tinggi suhu makin besar kontraksiMakin tinggi suhu makin besar kontraksi
3.3. pHpHMakin rendah pH makin rendah Makin rendah pH makin rendah kontraksikontraksi
4.4. FatiqueFatiqueOtot lemah kontraksi juga lemahOtot lemah kontraksi juga lemah
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TONUSTONUS
- Yaitu kontraksi partial karena discharge Yaitu kontraksi partial karena discharge motor neuron, dan karena rangsangan motor neuron, dan karena rangsangan subliminal pada serat otot terus menerus.subliminal pada serat otot terus menerus.
- Tegangan di dalam otot yang disebabkan Tegangan di dalam otot yang disebabkan kontraksi partialkontraksi partial
MACAM KONTRAKSIMACAM KONTRAKSI
1.1. IsotonicIsotonicPanjang otot berbedaPanjang otot berbeda
2.2. IsometricIsometricTonus otot berubahTonus otot berubah
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RASIO NEURONRASIO NEURON
SERAT OTOTSERAT OTOT
Rasio <, gerakan kasarRasio <, gerakan kasar
Rasio >, gerakan halus, misal ujung Rasio >, gerakan halus, misal ujung jarijari
Besar kecilnya rasio tergantung dari Besar kecilnya rasio tergantung dari macam serat otot yang dilayanimacam serat otot yang dilayani
4.4. FibrilationFibrilationKontraksi terus-menerus yang patologisKontraksi terus-menerus yang patologis
5.5. FasciculationFasciculationKontraksi terus-menerus yang fisiologis tapi Kontraksi terus-menerus yang fisiologis tapi sinkron, misalnya menggigil, ketakutansinkron, misalnya menggigil, ketakutan
6.6. Myasthenia gravisMyasthenia gravisKelemahan kontraksi otot karena kelainan Kelemahan kontraksi otot karena kelainan sinaps pada neuromuscular junctionsinaps pada neuromuscular junction
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CHAPTER #3CHAPTER #3
• Smooth muscleSmooth muscle
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Smooth Muscle - OverviewSmooth Muscle - Overview
• found in the walls of the hollow internal found in the walls of the hollow internal organs (e.g. blood vessels, bladder, GIT, organs (e.g. blood vessels, bladder, GIT, and uterus)and uterus)
• under control of the ANS = cannot be under control of the ANS = cannot be controlled consciously =involuntary controlled consciously =involuntary (one (one exception may be urinary bladder?)exception may be urinary bladder?)
• non-striated non-striated (I.e. smooth),(I.e. smooth), spindle-shaped spindle-shaped cells with one central nucleuscells with one central nucleus
• Lack sacromeresLack sacromeres• contracts slowly and rhythmically contracts slowly and rhythmically
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Smooth Muscle con’tSmooth Muscle con’t• Primarily supports visceral functions rather Primarily supports visceral functions rather
than locomotion & other behaviorthan locomotion & other behavior
• Some similarities & differences from both Some similarities & differences from both cardiac and skeletal muscles - can be cardiac and skeletal muscles - can be divided into subclasses each differentdivided into subclasses each different
• Some can produce more force per cross-Some can produce more force per cross-sectional area than striated muscles and sectional area than striated muscles and some can generate prolonged contractions some can generate prolonged contractions that require much less energy per unit time that require much less energy per unit time than striated musclethan striated muscle
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Smooth Muscle con’tSmooth Muscle con’t
• Sliding-filament theory appliesSliding-filament theory applies• Generally with little or no SR & lack Generally with little or no SR & lack
T-tubulesT-tubules• Rather than sacromere organization Rather than sacromere organization
= gathered into bundles of thick and = gathered into bundles of thick and thin filaments anchored in structures thin filaments anchored in structures called called dense bodiesdense bodies or connect to or connect to inside surface of plasma membrane inside surface of plasma membrane at sites called at sites called attachment plaquesattachment plaques
elongated and tapered at both ends – elongated and tapered at both ends – coupled with one another thru’ coupled with one another thru’ electrically conducting gap junctions – electrically conducting gap junctions – activation of a few fibers can generate activation of a few fibers can generate contraction that moves thru’out the contraction that moves thru’out the entire organ in a wave e.g. peristalsis entire organ in a wave e.g. peristalsis in GIT pushing food along – called in GIT pushing food along – called single-unit because entire set of fibers single-unit because entire set of fibers behaves as a unit rather than a set of behaves as a unit rather than a set of independently controlled fibersindependently controlled fibers
2.2. Multi-unit smooth musclesMulti-unit smooth muscles – act – act independently & contract only when independently & contract only when stimulated by neurons or in some stimulated by neurons or in some cases hormones = contraction is cases hormones = contraction is neurogenic – not coupled to one neurogenic – not coupled to one another by gap junctions e.g. muscles another by gap junctions e.g. muscles regulate diameter of pupil in iris and regulate diameter of pupil in iris and those in walls of blood vesselsthose in walls of blood vessels
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Smooth Muscles con’tSmooth Muscles con’t• Synapses of autonomic neurons with Synapses of autonomic neurons with
smooth muscle fibers are different from smooth muscle fibers are different from endplates formed by motor neurons = endplates formed by motor neurons = NT released from many swellings called NT released from many swellings called varicositiesvaricosities along length of autonomic along length of autonomic axons – diffuses over some distance axons – diffuses over some distance encountering many smooth muscle cells encountering many smooth muscle cells along the way – receptor molecules on along the way – receptor molecules on smooth muscle cells appear to be smooth muscle cells appear to be distributed diffusely over the cell surfacedistributed diffusely over the cell surface
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Regulation of Smooth Regulation of Smooth Muscle ContractionMuscle Contraction
• As in striated muscles, cyclic binding & As in striated muscles, cyclic binding & unbinding of myosin & actin myofilaments unbinding of myosin & actin myofilaments depends on presence of free Ca2+ in depends on presence of free Ca2+ in cytoplasmcytoplasm
• Contract & relax Contract & relax more slowlymore slowly than striated than striated muscles & are capable of muscles & are capable of more sustained more sustained contractioncontraction
• Slow release & uptake of Ca2+ associated Slow release & uptake of Ca2+ associated with relatively with relatively underdeveloped SRunderdeveloped SR (composed (composed only of smooth, flat vesicles located close to only of smooth, flat vesicles located close to inner surface of plasma membrane) inner surface of plasma membrane)
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Regulation of Smooth Regulation of Smooth Muscles con’tMuscles con’t
• because of elongated shape = no point in because of elongated shape = no point in cytoplasm is > few micrometers away cytoplasm is > few micrometers away from plasma membrane = diffusion of from plasma membrane = diffusion of Ca2+ between membrane & Ca2+ between membrane & myofilaments is sufficient for regulating myofilaments is sufficient for regulating slow contraction & plasma membrane slow contraction & plasma membrane cells performs Ca-regulating function cells performs Ca-regulating function similar to those of SR in striated musclesimilar to those of SR in striated muscle
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Regulation of Smooth Regulation of Smooth Muscle con’t Muscle con’t
• In striated muscle, troponin & tropomysin control In striated muscle, troponin & tropomysin control access to myosin binding sites however, smooth access to myosin binding sites however, smooth muscles muscles lacklack troponin but have the filamentous troponin but have the filamentous protein protein caldesmoncaldesmon = binds to thin filaments = binds to thin filaments preventing binding between myosin & actinpreventing binding between myosin & actin
• Caldesmon removed by 2 mechanisms:Caldesmon removed by 2 mechanisms:1.1. CalmodulinCalmodulin = Ca2+ binding protein & when = Ca2+ binding protein & when
calmodulin/Ca2+ complex binds to caldesmon, calmodulin/Ca2+ complex binds to caldesmon, myosin cross-bridges are permitted to bind to thin myosin cross-bridges are permitted to bind to thin filaments ORfilaments OR
2.2. Caldesmon may be phosphorylated by Caldesmon may be phosphorylated by protein kinase protein kinase CC (when phosphorylated can’t bind to thin filaments = (when phosphorylated can’t bind to thin filaments = doesn’t inhibit myosin-actin interactions)doesn’t inhibit myosin-actin interactions)
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Regulation of force
Smooth muscles have a multiplicity of mechanisms to vary force development.
One smooth muscle differs from another by the particular mechanisms
employed
The final common pathway in nearly all smooth muscles is regulation of the
intracellular [Ca2+].
An increase of [Ca2+] results from either release from intracellular stores or
from transmembrane flux.
Force can also be regulated by regulating the degree of myosin light chain
phosphorylation.
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neurotransmitter or hormone
2nd messengerscAMP, IP3
R R
Ca2+ Ca2+
voltage-operated ion channel
ion exchangers and pumps
ATP ATP
Ca2+Ca2+ Na+ Na+
K+
Ca2+ contractionCa2+s.r.
phosphorylation of myosin
regulation of kinases,
phosphatases
cGMP
A multiplicity of mechanisms
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Electrophysiological control of contraction
Action potentials generate twitches or tetanic contractions
Tonic activity can be related to slow membrane potential changes
Em
T
Action potentials and twitches can be superimposed on rhythmical activity