Outline Cellular Movement and Muscles:
Cytoskeleton and Motor Proteins -
-
All All Phy Physi sio o pro proce cess sses es dep depen end d on on movement: Intracellular transport o o Cell shape Cell motility o o Animal locomotion All All mvmt mvmt depe depend nd on on same same mac machi hine nery ry
//01234// Microtubules: Composition and 5ormation 5ormation -
Micr Microt otub ubul ules es are are pol polym ymers ers o" o" the the prot protei ein n tubulin #ubulin #ubulin o (imer o" 6 – tubulin and 7 – tubulin 5orms spontaneously +no enyme needed, o Polarity 4 ends are di8erent + - , 9 + , end
Cytoskeleton -
E!. Movement o" pi!ment !ranules
Prot Protei ein n – bas based ed int intra race cell llul ular ar net netwo work rk
Motor Proteins
-
Enym Enymes es that that use ener ener!y !y "rom "rom A#P to move
Cytoskeleton use "or movement -
-
Cyto Cytosk skel elet eto on ele eleme ment nts s o Microtubules o Micro$laments % way ways s to to use use cyto cytosk skel elet eton on "or "or movement: o Cytoskel and motor protein carriers o #o #o reor!anie reor!anie cytoskeletal cytoskeletal network o Motor proteins pull on cytoskeletal cytoskeletal &rope'
Cytoskeleton and Motor Protein (iversity -
)tru )truct ctura urall and and "unc "uncti tion onal al dive divers rsit ity y o Many iso"orms o" cytoskeletal and motor proteins *arious ways o" or!aniin! o cytoskeletal cytoskeletal elements o Alteration o" cytoskeletal and motor protein "unction
Microtubules -
-
#ubel ubelik ike e poly polyme mers rs o" pro prote tein in tubu tubuli lin n o Multiple iso"orms Anc Anchor hored at both both ends nds o Microtubule – or!aniation center +M#OC, +-, near nucleus o Attached to inte!ral proteins +, in plasma membrane Moto Mo torr prot protei eins ns tra trans nspo port rt sub subce cell llul ular ar components alon! microtubules o Motor proteins like kinesin and dynein
Microtubule Assembly -
-
Acti Activa vati tion on o" #ubul ubulin in by #P Mono Mo nom mer mon mono omer mer ; dimer imer (imers "orm sin!le – stranded proto$lament Proto oto$la $lament ment "o "orm shee sheett )hee )heett rol rolls ls up to "orm "orm a tub tubul ule e (ime (imers rs adde added d or or remo remove ved d "ro "rom m end ends s o Asymmetrical !rowth o rowth is "aster at end Cell Ce ll re!u re!ula late tes s rat rates es o" !row !rowth th and and shrinka!e
2% 1 234 Microtubule rowth and )hrinka!e -
-
-
5acto actors rs a8e a8ect ctin! in! !row !rowth th1s 1shri hrink nka! a!e e o Concentration o" tubulin o
ol and colchicines +plant o poisons,
Movement alon! microtubules -
Motorr prot Moto protei eins ns mov move e alon alon! ! micr microt otub ubul ules es (ire (irect ctio ion n dete determ rmin ined ed by by pola polari rity ty and and motor protein type o ?inesin move in +, direction (ynein move in +-, direction +lar!er o than kinesin and @> "aster,
-
Movement "ueled by hydrolysis o" A#P ate o" movement determined by A#Pase o" motor protein and re!ulatory proteins
2B1234
-
Cilia -
umerous wavelike motion
Assembly and disassembly occur simultaneously and overall len!th is constant Cappin! Proteins o Increase len!th by stabiliin! – end and slowin! disassembly o
41234
5la!ella -
)in!le or in pairs whiplike movement
C 9 5 composed o" microtubules arran!ed into a>oneme -
Dundle o" parallel microtubules B pairs o" microtubules around central pair o B4
Asymmetric activation o" dynein causes movement Microtubules and Physiolo!y Cellular Process Cytokinesis
Physio ">n (evt 9 rowth +mitosis, A>on )tructure ervous system *esicle #ransport
Micro$lament +Actin Arran!ement, Arran!ement o" Micro$laments in the cell -
-
#an!led networks o Micro$laments linked by $lamin protein Dundles o Cross-linked by "ascin protein
etworks and bundles o" micro$laments are attached to cell membrane by dystrophin protein -
Maintain cell shape used "or movement
Movement by Actin Polymeriation -
4 types o" amoeboid movement o 5ilapodia are rodlike e>tensions o" cell membrane eural connections Microvilli o" di!estive epithelia o =amellapodia are sheetlike e>tensions o" c. membrane =eukocytes Macropha!es
Micro$laments -
Polymers composed o" actin In eukaryotic cells Gses motor protein myosin Movement arises "rom: o Actin polymeriation o )lidin! $laments usin! myosin
Micro$lament )tructure and rowth -
- actin monomers polymerie to "orm 5actin )pontaneous !rowth o H-23 times "aster at end #readmillin!
%J1234 Actin Myosin ; Motor Protein Myosin -
-
-
Actin – based movements involve motor protein myosin o )lidin! 5ilament Model Myosin is an A#Pase o Converts ener!y "rom A#P to mech. Ener!y 2 classes o" myosin o Many iso"orms in each class All iso"orms have similar structure o
#ail +bind to subcellular components, eck +re!ulation o" A#Pase,
)lidin! 5ilament Model +J31234, -
Pullin! rope sort o" o Actin – ope o Myosin – Arm
Muscle Cells +Myocytes, -
Myocytes +muscle cells, o Contractile cells uniKue to animals Contractile elements within myocytes o #hick 5ilaments Polymers o" myosin Myosin II he>amers
-
4 Processes: o Chemical eaction Myosin binds to actin +cross – brid!e, o )tructural Chan!e Myosin bends +power stroke, Cross brid!e cycle o 5ormation o" cross brid!eF power strokeF release and e>tension A#P to release and reattach to actin o Absence o" A#P causes ri!or mortis =O= Myosin cannot release actin
o
-
-
#hin 5ilaments Polymers o" alpha – actin Ends capped by tropomodulin and CapL to stabilie #roponin and tropomyosin on outer sur"ace
Muscle Cells -
Actino – Myosin Activity
4 main types o" muscle cells are based on arran!ement o" actin and myosin o )triated +striped appearance, )keletal and cardiac Actin and myosin arran!ed in parallel o )mooth +do not appear striped, Actin and myosin are not arran!ed in any particular way
4 5actors a8ectin! mvmt -
Gnitary (isplacement (istance Myosin steps durin! each o cross – brid!e cycle o (epends on: Myosin neck len!th =ocation o" bindin! sites on actin
)triated and Muscle #ypes +JB1234, IMP#
•
-
)triated Muscle )tructure -
Actin and Myosin 5unction Cell Process *esicle #ransport Microvilli Amoeboid movement )keletal muscle contraction Cardiac muscle contraction )mooth muscle contraction
Physio ">n
#hick and thin $laments arran!ed into sarcomeres epeated in parallel in series o )ide by side across myocyte Causes striated appearance End to end alon! myocyte o
)arcomeres -
-
L – disk o Dorder o" each sarcomere o #hin $laments attached to -disk and e>tend "rom it towards middle o" sarcomere A – band o Middle re!ion o" sarcomere o Occupied by thick $laments
-
I – band o On either side o" L – disk o Occupied by thin $lament
Contraction and ela>ation in *ertebrate )triated Muscle e!ulation o" Contraction
@41234 )arcomeres -
#hick $lament surrounded by H thin $laments %( – or!. o" thin and thick $laments is maintained by other proteins o ebulin Alon! len!th o" thin $lament
E>citation – Contraction Couplin! +EC couplin!, o (epolariation o" sarcolemma o Elevation o" intracellular Ca 4 o Contraction )lidin! $laments
Ca4 Allows myosin to bind to actin
o
#itin
?eeps thick $lament centered in sarcomere Attaches thick $lament to L – disk
-
Muscle Actinomyosin Activity is GniKue -
-
Myosin II cannot dri"t away "rom actin (uty Cycle o" Myosin II is 3.3@ +O# 3.@, o
Contractile 5orce -
(epends on overlap o" thick and thin $laments o More overlap N more "orce o Amt. o" overlap depends on sarcomere len!th Measured by distance between – disks Ma>imal "orce occurs at optimal len!th o (ecreased "orce ; shorter1lon!er len!ths
#roponin and #ropomyosin H@1234 #roponin – tropomyosin iso"orms -
-
Myo$bril -
At restF cytoplasmic ca4 is low o #roponin – tropomyosin cover myosin bindin! sites on actin As cytoplasmic ca4 increases o Ca4 binds to #nC +calcium bindin! site on troponin, o #roponin – tropomyosin movesF e>posin! myosin – bindin! site on actin o Myosin binds to actin and cross brid!e cycle be!ins o Cycles continue as lon! as Ca4 present o Cell rela>es when sarcolemma repolaries and intracellular Ca4 returns to restin! levels
Properties o" iso"orms a8ect contraction o "#nC has hi!her anity "or Ca4 than s1c#nC mucles with "#nC respond to smaller increases in cytoplasmic Ca4 Iso"orms di8er in a8ect o" temp. and p<
-
Myosin and Iso"orms
In musclesF sarcomeres are arran!ed into myo$brils )in!leF linear continuous stretch o" o interconnected sarcomeres o E>tends len!th o" muscle cell o Parallel arran!ement more myo$brils in parallel ; !enerate more "orce
-
Properties o" iso"orms a8ect contraction o Iso"orms o" myosin II in muscle Iso"orms can chan!e over time o
H1234 MQO)I I)O5OM) IMP# E>citation o" *ertebrate )triated Muscle -
)keletal muscle and cardiac muscle di8er in e>citation and EC couplin!
-
(i8erences: o Cause o" depolariation o #ime chan!e in membrane potential o Propa!ation o" AP o Cellular ori!in o" Ca4
-
Action Potential -
APs alon! sarcolemma si!nal contraction o a enters cell when a channels open (epolariation o *olta!e – !ated Ca4 channel open Increased Ca4
o o
a channels close ? leave cell when ? channels open epolariation eestablishment o" ion !radients by a1? A#Pase and Ca4 A#Pase
Channels allow Ca4 enter cytoplasm o Ca4 channels in cell membrane (ihydropyridine receptor +(chan!er +aCaS, o Ca4 #ransporters in ) membrane Ca4 A#Pase +)ECA,
Induction o" Ca4 elease "rom )
o
-
Initial Cause o" (epolariation -
-
AP alon! sarcolemma conducted down # #ubules o (epolariation depends on (
tracellular Tuid In heartN increase in Ca4 causes y to openN allowin! release "rom ) Ca4 induced Ca4 release In skeletal muscle F chan!e in (
Myo!enic +be!innin! in muscle, o )pontaneous Pacemaker cells o Cells depolarie "astest o Gnstable restin! membrane potential euro!enic +be!innin! in the nerve, o E>cited by neurotransmitter "rom motor nerves )keletal muscle o Can have multiple +tonic, or sin!le +twitch, innervations sites
•
•
B1234 9 031234 IMP# # – tubules and )arcoplasmic eticulum ela>ation -
-
-
#ransverse #ubules +#-tubules, o Inva!inations o" sarcolemma o Enhance penetration o" AP into myocyte o (eveloped in lar!erF "aster twitchin! muscles o =ess developed in cardiac muscle )arcoplasmic eticulum +), o )tores Ca4 bound to protein seKuestrin #erminal cisternae increase stora!e o # – tubules and terminal cisternae are adRacent to one another
Ca4 Channels and #ransporters
-
epolariation o" )arcolemma emove Ca4 "rom cytoplasm Ca4 A#Pase in sarcolemma and o ) o a1Ca4 e>chan!er +aCaS, in sarcolemma o Parvalbumin Cytosolic Ca4 bindin! protein bu8ers Ca4 Ca4 dissociates "rom troponin #ropomyosin blocks myosin bindin! sites Myosin can no lon!er bind to actin 041234
-
)ummary o" )triated Muscles
-
0%1 234 )mooth Muscle -
-
)lowF prolon!ed contractions O"ten "ound in wall o" tubes in body Dlood vesselsF intestineF airway etc o (i8erences "rom )keletal Muscle: o o sarcomeres + no striations, #hick and thin $laments are scattered in cell Attached to cell membrane at adhesion plaKues o o #-#ubules and minimal ) o O"ten connected by !ap Runctions 5unction as a sin!le unit o (i8erent mechanism o" EC couplin!
Chan!in! 5iber #ypes: -
*ariation in other properties o" muscle cells Myo!lobin content o o umber o" mitochondria )keletal muscle cells can be classi$ed as "astF slowF whiteF redF o>idativeF !lycolytic
-
-
(evelopmental +"rom embryo to adult, o Increased proportion o" "ast muscle iso"orms Physiolo!ical response o E>ercise o Can chan!e both cardiac and skeletal muscle Chan!es due to hormonal and nonhormonal mechanisms o #hyroid hormones repress e>pression o" D-myosin II !ene and induce alpha – myosin II !ene Alpha – myosin II e>hibits the "astest action-myosin A#Pase rates o 5or e>ampleF direct stimulation o" cell can alter !ene e>pression
Control o" )mooth Muscle Contraction -
e!ulated by nerves hormones and physical conditions o At rest the protein caldesmon is bound to actin and blocks myosin bindin! )mooth muscle does not have troponin )timulation o" cell increases o intracellular Ca4 o Ca4 binds to calmodulin Calmodulin binds caldesmon and removes it "rom actin Cross-brid!es "orm and contraction occurs Calmodulin also causes phosphorylation o" myosin Increase in myosin A#Pase activity
BJ1234 #rans – di8erentiation o" Muscle Cells -
•
•
•
•
0B1234 PUI(I (iversity o" Muscle 5ibers -
(i8erent protein iso"orms a8ect EC couplin! Ion channels o o Ion pumps Ca4 bindin! proteins o o )peed o" myosin A#Pase
#rans – di8erentiation o Cells used "or novel "unctions o 5or e>ampleF heater or!ans o" bill$sh eye )pecialied muscle cells 5ew myo$brils +little actin and myosin, Abundant ) and mitochondria 5utile cycle o" Ca4 in and out o" the )
Invertebrate Muscles -
*ariation in Contraction 5orce due to !raded e>citatory postsynaptic potentials +EP)P, o Innervations by multiple neurons o EP)Ps can summate to !ive stron!er contraction
o
)ome nerve si!nals can be inhibitory
•
Asynchronous insect 5li!ht muscles -
-
Uin! beats 4@3 – 2333< o 5astest vertebrate contraction ; 233< +toad$sh, Asynchronous muscle contractions o Contraction is not synchronied to nerve stimulation o )tretch – activation )ensitivity o" myo$bril to Ca4 chan!es durin! contraction1 rela>ation cycle Intracellular Ca4 remains hi!h Contracted muscle is Ca4 insensitive
•
Muscle rela>es )tretched muscle is Ca4 sensitive o Muscle contracts o
Mollusc +Divalve, Catch Muscle -
Muscle that holds shell closed Capable o" lon! duration contractions with little ener!y consumption o Protein twitchin may stabilie actinmyosin cross-brid!es Cross – brid!es do not continue to cycle Phosphorylation1dephophoryl ation o" twitchin re!ulates its "unction