Lecture 5-7 Flashcards
Myofilament
Actin and myosin filaments that make up a sarcomere
Myofibrils
A chain of sarcomeres w/in a myofiber
Myofiber
Individual multinucelated muscle cell
Sarcolemma
Cell membrane of muscle fiber
Endomysium
Delicate CT around each myofiber
Fascicle
A bundle of myofibers
Perimysium
CT surrounding individual Fascicle
Muscle
Made up of fascicles “bundle of sticks”
Epimysium
CT surrounding entire muscle
Z discs [lines]
Anchor actin filaments
Located at each end of a sarcomere
Z-between
I bands
Composed entirely of actin
Width changes during contraction
A bands
Actin and myosin
With doesn’t change during contraction
H bands
Composed entirely of myosin
Width changes during contraction
How many t-tubules to sarcomere?
2 t tubules to a sarcomere
Changes that occur during sarcomere contraction
HI changes
A band doesn’t change
Sliding filament mechanism events:
- AP at terminal end of nerve fiber
- Opening of voltage-gated Ca++ channels o nerve fiber ending
- Release of Ach from synaptic vesicles into synaptic cleft
- Opening of ligand-gated Na+ channels of sarcolemma
- Generation of AP on sarcolemma
- Voltage-gated channels on T tubules interact w/ ryanodine receptors on SR
- Opening of ryanodine-sensitive Ca+ ion release channels
- increase Ca++ [ ] in cytosol
- Activation of sliding filament mechanism
- released Ca+ binds to troponin.
- Tropomyosin uncovers myosin binding sites on actin.
- ATPase heads of myosin molecules split ATP and bind to actin.
- Stored energy in myosin head causes deformation so that thick /thin filaments slide past one another
- A 2nd ATP binds to myosin and causes it to release actin.
- Repeated over and over
- Contractions ends when ATP-dependent Ca+ pump gets Ca+ back to SR.
Does binding of myosin head or release of myosin head req’ ATP?
Release after the powerstroke
Describe role of SR and T tubules in muscle contraction:
T-tubules: When depolarizer by AP, conformational change in DHP receptor and ryanodine receptor= opening of ryanodine Ca+ channels
SR: Ca+ released after its ryanodine receptor is opened by DHP on T tubule
Role of Ca++ in muscle contraction
Ca+ binds to troponin which allows tropomyosin to uncover myosin binding sites on actin—–
Exposes active site
Function of SERCA
Sarcoplasmic reticulum Ca++ ATPase: recycles Ca++ against [ ] gradient…ATP-dependent.
Function of calsequestrin
Takes Ca+ out of sol’n makes job easier for SERCA…
Lessens the [] of Ca++gradient to lower resistance
Function of DHP
Voltage gated L-type calcium channels arranged in quadruplets
On sarcolemma of t tubules; conformational change results in opening of SR ryanodine channels allowing Ca++ into the cytosol
Function of ryanodine channels
Allow Ca+ to flow into cytosol to initiate muscle contraction…must be activated by DHP
Preload
load on a muscle in the relaxed state
Results: passive tension-stretching
Afterload
Load the muscle works against
Results: if more force is generated than afterload =isotonic contraction
If muscle generates less force than afterload=. Isometric contraction
Active vs passive tension
Active: produced by cross-bridge cycling-contraction
Passive: produced by preload
What is meant by cross-bridge cycling?
Contraction is the continuous cycling of cross-bridging. ATP is not req’d to form the cross-bridge linking to actin but is req’d to break the link w/ actin.
Muscle length-tension relative to changes in sarcomere length…why?
Length
- 5microm —0 tension
- 2—Max. Tension
- 65—max. Tension
Where is ATP req’d for muscle contraction
Most used during sliding filament mechanism
Pumping Ca++ from sarcoplasm to SR.
Pumping Na+ and K+ through the sarcolemma to reestablish resting potential
Sources of rephosphorylation during muscle contraction and significance:
Phosphocreatine: releases energy rapidly…reconstitutes ATP.. ATP+phosphocreatine =5-8 sec of contraction
Glycolysis: Lactic acid build-up
Can sustain contraction for 1 minute
Oxidative metabolism: Provides > 95% energy needed for long-term contraction.
Compare isotonic and isometric contractions
Isometric:
Increase in tension but not length…ex: wall sit
Isotonic:
Muscle length changes…ex: push-up
Concentric isotonic muscle contraction
Contraction when muscle shortens
Eccentric isotonic muscle contraction
Contraction when the muscle lengthens
Fast fibers-light fibers
Contract rapidly but have less endurance
Fewer mito. –primarily anaerobic resp.
Little myoglobin, LARGER [ ] of ATPase
Slow fibers-dark fibers
Contract slowly but more endurance
More mito. -use aerobic resp.
More myoglobin..smaller [ ] of ATPase
Define motor unit
A neuron and the myofibers it innervates makes up a motor unit.
Summation
Additional spike can occur before the previous Ca++ ions have been returned to the SR.
Increase in Total amt. Ca++ in cytosol and increases the rate of cycling btw myosin and actin cross-bridging.
Leading up to tetany…motor units are becoming locked up
Tetany
Muscle remains at maximal contraction. No time for relaxation btw spikes
3 types of lever systems:
1st, 2nd, and 3rd class
1st class muscle lever system
Fulcrum in the middle
Ex: seesaw
In and out force move in OPPO directions
2nd class muscle lever system
resistance is in the middle
Ex: wheelbarrow
Both in and out force on same side of fulcrum
3rd class muscle lever system
Effort [in-force] is in the middle
Ex: lifting a weight in palm
Both forces are same side of fulcrum
Describe cellular characteristics of single axon
Many mito. Synaptic vesicles w/ Ach
Dense bars
Synaptic gutter
Synaptic cleft
How many Ach released via exocytosis:
300,000
Dense bars
Anchored to the presynaptic membrane and asso. W/ synaptic vesicles to which they are tethered by short filaments
Hypothesis: help guide exocytosis…not truly known.
Synaptic gutter(trough)
Groove or furrows in the surface of a sarcolemma in which the axon terminal makes contact w/ the sarcolemma
Subneural clefts are smaller clefts in the bottome of the synaptic trough.
Synaptic cleft
20-30 nm wide
Narrow but real gap btw the axolemma of the axon terminal and the sarcolemma of the innervated muscle fiber.
structure of Ach gated channel
Sarcolemma of skeletal muscle:
- has Ach-gated channels
- 275,000mw
- 2 alpha,1 beta,1 gamma, and 1 delta protein
- tubular channel remains closed until 2 Ach molecules attach to its alpha subunits
Which subunit does Ach attach?
Must attach to the 2 alpha proteins to open channels
Where are vesicles for neurotransmitters formed in the neuron? How are they transported?
Formed in the Golgi and are carried by axonal transport to axon terminus -this is where they are filled w/ Ach
Compare Ca++ [ ]outside and inside the axoplasm:
[Ca++] =
ECF: 1-2 mM
Intracellular:
How does calcium enter the axon during the transmission of an action potential
When AP arrives at the terminus of the axon, voltage gated channels open and Ca+ enter axon terminus…
AP activates dihydropyridine channels and the conformational Change allows Ca+ to flow out of ryanodine channels
Number of Ach molecules that attach to each ligand gated channel?
125 vesicles fuse to the neuronal membrane and empty their contents into the synaptic cleft
Define end plate potential
Created by large numbers of Na+ to pass through muscle fiber membrane…[50-75mV] initiates a AP on the sarcolemma
Steps in skeletal muscle contraction beginning w/ release of Ach from neuron:
1: Release of Ach into synaptic cleft
2: diffusion across cleft
3: Binding of Ach to Ach receptors on sarcolemma
4: opening ligand-gated channels
5: Na+ influx
6: End plate depolarization
7: Opening of voltage gated Na+ channels—>sarcolemma AP
8: depolarization of T-tubule
9: conformational change in DHP receptor –>change in ryanodine
10: Ca+ release from SR d/t open ryanodine channels
11: Ca+ [ ] increase in cytosol
12: binding of Ca+ to troponin C
13: Conformational change in troponin
14: Tropomyosin is pulled away from active sites on actin-exposure
15: binding of myosin heads to actin active sites
How is Ach removed from synaptic cleft? Acetylcholinesterase?
Degradation into choline and acetate by aceytlcholinesterase
Resp take of choline by axon end terminal
Diffusion of Ach away from site.
Drugs that mimic Ach but are not broken down by aceytlcholinesterase and describe their effect on muscle contraction:
Methacholine, carbachol, and nicotine:
same effect on muscle fiber as Ach, but aren’t broken down byacteylcholinesterase-cause spasm
Neostigmine, physostigmine, and diisopropyl flourophosphates:
Inactivate acetylcholinesterase- cause spasm
Curare:
Prevents passage of impulses from nerve ending into muscle-cause paralysis
Cause of myasthenia gravis and effects:
Autoimmune disease where antibodies attack Ach recptors…End plate potentials are too weak to initiate opening of the voltage-gated Na+ channels.
Effects: muscle weakness/spasm
How neostigmine alleviate effects of MG?
Inactivated aceytlcholinesterase to allow movement
Tricuspid valve
3 leaf valve on R side
Bicuspid/mitral valve
2 leaf valve on L side
Cardiac muscle tissue vs. skeletal
Cardiac:
Syncytium- 1 cell coupled to a neighbor via gap junctions
Striated[ skeletal also], mononucleated, intercalated discs, and cell branching did
T tubules in skeletal and cardiac fibers
Skeletal: at the ends of thick filaments. 2 cisternae, triads w/ SR. SR more extensive.
Cardiac: along the Z line. One cisterna per T, form diads w/ SR. SR is less extensive
Fast cardiac muscle APs:
Fast: found in atria,ventricles, and conduction system
Rapidly conducting but non-contractile in purkinje fibers
Rapidly conducting and contractile in atrial and ventricular fibers
High amplitude [100mV]
Slow cardiac muscle AP’s
Found in SA and AV nodal tissues
Conducts slowly
Automatically depolarizes during resting phase-faster in SA[why it’s pacemaker]
Low Amplitude [60mV]
Five phases of cardiac muscle AP
Phase 4: resting Phase 0: rapid depolarization Phase 1: initial, incomplete repolarization Phase2: plateau or slow decline of membrane potential Phase 3: Repolarization 1 I\_2_ I. \ 0 I \ 3 _I \\_\_\_\_\_4
Fast action potentials
D/t changes in conductance of K+,Na+, and Ca+
Conductance pattern is mostly d.t voltage dependent gates
Greater AP amp. , rapid rate of rise of phase 0, and larger cell diameter result in faster conduction velocity
Slow AP
No fast Na+ ion gates
Upstroke (- to +) of AP is due to Ca+—slow!
Resting phase potential 4 is close to -60mV rather than -90mV[fast AP]
Change in potential is less than fast
SA and AV nodal tissue will spontaneously depolarize slowly to reach threshold during phase 4
Characteristics of fast type contractile myocytes:
Large diameter
High amplitude
Rapid onset of AP
Characteristics of fast type non-contractile myocytes:
VERY large diameter
VERY rapid upstroke
Characteristics of slow type non-contractile myocytes:
small diameter
Low amplitude
Slow rate of depolarization
Role of ions in creation of cardiac muscle AP
Action potential plateau:
NA+ channels close rapidly [like skeletal] BUT the Ca++ channels open slowly and stay open for a longer period.
There is a delay in the opening of the K+ channels
the large [ ] of both Ca+ and K+ are responsible for the plateau.
SA node is pacemaker b/c
It’s depolarization occurs more rapidly than any other and reaches threshold first. THis becomes the norm rhythm.
APs that originate anywhere besides SA node are called:
Ectopic
Resting membrane potential for SA node fiber:
-55mV to -60mV [threshold-40mV]
Phase 4: slow depolarization: d/t inactivated fast Na+ gates, only slow Na+-Ca+ channels open [slow leak of Na+ ions back into cells]-membrane potential becomes more positive. At -40mV Sodium-calcium channels become activated
Large # of K+ channels open when Na+-Ca+ channels become inactivated…nodal cells become repolarized.
Ventricular resting membrane potential
-85 to -90 mV
Atrial AP sequence
Phase 4: resting potential is gradual to
Phase 0: Ca+ influx
Phase 1and 2not noted
Phase 3: K+ efflux [cell becomes more - again
Ventricular AP sequence
phase 4: resting -90mV Phase 0: depolarization rapid Na+ influx Phase 1: fast K+ efflux Phase 2: Ca+ influx and K+ efflux Phase 3:Delayed K+ efflux
Faster the ion channels return to phase 4,
the shorter the refractory period
Sinus rhythm
Originates in SA
Mechanism of Ca+ release during contraction of cardiomyocyte w/ DHP and Ryanodine compared to skeletal muscle.
AP travels along sarcolemma to T-tubules
Ca+ enters from the ECF through voltage-dependent Ca+ channels (DHP) of T-tubule
ELevated cytosolic Ca+ triggers more CA+ to enter from cisternae of the sarcoplasmic tubules though ryanodine receptors
Elevated Ca++ binds to troponin and results in myofilament contraction
Skeletal muscle Req’s conformational change in DHP and ryanodine receptor for influx of ICF ca++
SERCA cardiac muscle relaxation
SR Ca+ ATPase
Stimulated by phosphorylation via an integral SR protein called phospholambian, which reduces its ability to inhibit SERCA pump
Returns Ca+ to SR during diastole
This allows for even greater Ca+ release on the next beat.
Also allows for a fast clearance of Ca+ from sarcoplasm.
Sodium-calcium exchanger in cardiac muscle relaxation
Transports Ca+out of the cell
Atria primer pumps
About 80% of blood flows from the atria to the ventricles before the atria contract
Atria can therefore add an additional 20% by contraction
Ventricular systole
AV valves closed during systole
End of ventricular systole
AV valves open at end of systole b/c of increased pressures in atria
Cardiac cycle
1st 1/3 diastole: rapid filling
Middle 1/3: small amt. blood flows into ventricles blood continues to flow into atria
Last 1/3:atria contract to push last 20% of blood into ventricles.
Isometric contraction: ventricles contract but semilunar valves do not open for .02-.03 s
Period of rapid ejection:
Occurs when L ventricular pressure is a little above 80 mmHg and R ventricular pressure is above 8 mmHg
Semilunar valves open.
About 70% blood ejected
Occurs during first 1/3 of ejection
Period of slow ejection
Remaining 30 % blood is ejected from ventricles
Occurs during the last 2/3 of ejection
Frank-starling law
More stretch =strongest contraction= most blood pumped into aorta
Stretching brings actin and myosin to optimum degree of overlap
Blood in proximal aorta
Mean velocity = 40cm/s
Flow is phasic
Velocity ranges form 120 cm/s (systole) to - value before aortic valves close in diastole. [- d/t backflow]
Blood in distal aorta and arteries
Velocity is greater in systole than diastole
Forward flow is continuous b/c of elastance of vessel walls during diastole
Forces altering flow
Active tissue may req’ 20-30X as much blood flow than at rest
CO can’t exceed 4-7x > at rest
Microvessels at each tissue monitor tissue needs–act directly on local blood vessels
Nervous control and hormones help tissue blood flow
