Test 3 Physiology 9.2, 12.1, 12.2

From Grace

4 special functional features of muscles

contractility, excitability, extensibility, elasticity

contractility

• muscle contracts forcefully

• cells shorten, generate pulling force

excitability

(can be electrically excited and generating AP)

• nerve signals or other factors excite muscle cells

• electrical impulse to travel along the cell’s plasma membrane

extensibility

* can be stretched to its normal resting length and beyond to a limited degree

elasticity

* if muscle cells are stretched, they recoil passively to their original resting length

muscle tissue

• composed of muscle cells

• elongated shape able to contract (shorten)

• myofilaments that contain actin and myosin

muscle cells

muscle fibers

myofilaments contain ____ __and__ ______

actin, myosin

functions of muscle tissue

• movement

• maintenance of posture

• joint stabilization

• heat generation

three types of muscle tissue

• skeletal

• cardiac

• smooth

skeletal: cell shape and appearance

single, very long, cylindrical, multinucleate cells with obvious striations

skeletal: body location

attaches to bones (or some facial muscles) to skin

cardiac: body location

walls of the heart

cardiac: cell shape and appearance

branching chains of cells; uni- or binucleate striations

smooth: body location

• single-unit muscle in walls of hollow visceral organs (other than heart)

• multiunit muscle in intrinsic eye muscles, airways, large arteries

smooth: cell shape and appearance

* single, fusiform, uninucleate, no striations

innervation

control is either voluntary or involuntary

muscle tissue characterized by __ __and__ ____

striations, innervation

voluntary

innervated by voluntary motor nerves, conscious control, somatic motor

involuntary

innervated by the autonomic nervous system

skeletal: cell characteristics

1. long and cylindrical, in bundles

2. multinucleate

3. obvious striations

• voluntary

• attached to bones, covered by fascia, skin

cardiac: cell characterstics

1. branching, chains of cells, rod shape

2. single or binucleated

3. striations

4. connected by intercalated discs

• involuntary

• myocardium - heart muscle

• pumps blood

smooth: cell charactristics

1. single cells, uninucleated

2. no striations

• involuntary

• lines hollow organs, blood vessels

• peristalsis

skeletal muscle makes up __% of body weight

40

skeletal muscle moves the _____

skeleton

what is the fastest type of muscle?

skeletal

what is the slowest type of muscle?

smooth

cells of __ __and__ ___ muscle are known as fibers; elongated

smooth, skeletal

muscle _____ depends on myofilaments

contraction

myofilaments

contractile proteins

2 kinds of myofilaments

actin and myosin

specialized for the storage of calcium

endoplasmic reticulum (ER)

connective tissue sheaths in skeletal muscle

epimysium, perimysium, endomysium

epimysium

outside the muscle

perimysium

around the muscle

* wrapped around fascicle

endomysium

within the muscle

* between individual muscle fibers

myofibril

• made up of repeating segments called sarcomeres

• basic unit of contraction

• dark areas called A bands are composed primarily of thick myosin filaments and lighter bands are thin actin filaments

dark areas called ___ ____ are composed of primarily thick myosin filaments

A bands

lighter areas are _

thin actin filaments

what are myofibrils?

• long rods within cytoplasm

• make up 80% of sarcoplasm

• are specialized contractile organelles

• are a long rod of repeating segments called sarcomeres

  • functional units of skeletal muscle tissue

  • responsible for contraction

what is a sarcomere?

basic unit of contraction of skeletal muscle

3 major “areas” of a sarcomere

1. Z disc (Z line)

2. thin (actin) filaments

3. thick (myosin) filaments

Z disc (Z line)

boundaries of each sarcomere

thin (actin) filaments

extend from Z disc toward the center of the sarcomere

thick (myosin) filaments

• located in the center of the sarcomere

• overlap with the thin filaments

• contain ATPase enzymes

sarcomere structure

• A bands

• I bands

• Z line

A bands

• both thick and thin filament (dark region)

• does not change during contraction

I bands

• only thin filament (light region)

• shortens during contraction

Z line

attachment site for thin filament

__ __and__ ___ create banding appearance

A bands and I bands

H zone

no thin filaments

M line

• center of H zone

• attachment site for thick filaments

sliding filament theory

• proposed by Hugh Huxley

• sliding of thick and thin filaments

• myosin heads: pivoting inward at hinge

• when muscle shortens:

  • H zone -- shortens

  • I band -- does not change

  • A band -- shortens

Crossbridge Cycle

1\. Myosin head bound to actin called crossbridge

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2\. ATP binds causing myosin head to detach from actin

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3\. Myosin hydrolyze ATP to ADP and Pi, releasing energy, myosin head energized

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4\. Myosin neck extends, moving myosin head forward, attaches to adjacent actin (ADP and Pi stay bound)

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5\. Pi release promote power stroke, myosin head pivots, actin is pulled forward called power stroke

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6\. ADP is released; myosin is able to bind to a new molecule of ATP to go through the CB cycle again

sliding filament model

• if no ATP available, myosin remains firmly attached to actin

• creates condition of rigor mortis

muscle innervation

• myelinated axon of motor neuron release action potential into axon terminal at neuromuscular junction

• in the axon terminal of a motor neuron --- synaptic vesicle containing acetylcholine releases across synaptic cleft

• acetylcholine crosses synaptic cleft to the junctional folds of the sarcolemma at the motor end plate

Cellular Regulation of Muscle Contraction

1. action

2. calcium transient

3. calcium binds troponin C

4. myosin power stroke

5. force production

How is cytosolic Ca elevated?

sarcoplasmic reticulum (SR)

intracellular Ca store

How is cytosolic Ca elevated?

ryanodine receptor (RyR)

SR Ca release channel protein

How is cytosolic Ca elevated?

SR Ca ATPase (SERCA)

Ca reuptake into SR

How is cytosolic Ca elevated?

• must increase Ca in cytosol for cell to contract

• need energy to move Ca back into SR → SERCA pump

• do NOT need energy to release Ca

How is RyR opened?

• L type Ca channel (DHP receptor): voltage sensitive Ca channel

• skeletal muscle: physical coupling with DHP

• cardiac muscle: Ca induce Ca release (CICR)

thin filaments

• troponin (Tn), 3 subunits

• tropomyosin

____ is the Ca sensor

TnC

TnC

Ca binding

Tnl

inhibitory subunit

when muscle relaxed

myosin-binding sites blocked

when myosin-binding sites exposed

Ca move tropomyosin so myosin can interact with actin

Contraction regulation by Ca2+

• striated muscles contract when Ca2+ levels increase within myofiber

• Ca2+ signal is transmitted to contractile apparatus by thin filament proteins troponin and tropomyosin

• when Ca2+ is low, the troponin-tropomyosin complex sits on the thin filament in a position that blocks actin’s binding site for myosin

• when Ca2+ rises, they roll out of the way, allowing myosin to bind to actin

• initiate the cross-bridge cycle

• when Ca2_ falls, troponin-TM block actin-myosin interaction again

Time Course of Depolarization

• cardiac and skeletal muscles have dramatic differences

  • in the shape of AP

  • in the duration of the AP

  • refractory periods

• muscle cells cannot depolarize again until the repolarization phase is complete

  • this window of insensitivity is called the effective refractory period

Time Course of Depolarization: Skeletal Timing

• skeletal myofibers: depolarize and repolarize very quickly

• AP: 2-5 ms

• contraction: 200-400 ms

  • skeletal muscle AP is similar to neuronal AP

skeletal or cardiac?

skeletal

Time Course of Depolarization: Skeletal

• AP contraction happens first

• AP has short duration

Skeletal Muscle: summation

• happens to skeletal muscle because of the short duration of AP

• twitch- 1

• wave summation - ~3

• unfused (incomplete) tetanus - ~5

• fused (complete) tetanus - infinite (plateau)

Time Course of Depolarization: Cardiomyocytes

• cardiomyocytes: depolarize quickly but take much longer to repolarize

• voltage-sensitive Ca2+ channels (LTCC) in cardiac muscle stay open for a much longer period

Skeletal or Cardiac?

cardiac

Time Course of Depolarization: Cardiac Muscle

• prolonged refractory period is critical for cardiac muscle

• inability to respond to further stimulation

• allows the ventricles sufficient time to empty their content and refill before the next cardiac contraction

Action Potential of Cardiac Muscles

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4\. Na+, Ca2+ channels closed, open K+ rectifier channels keep TMP stable at -90mV

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0\. Rapid Na+ influx through open fast Na+ channels

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1\. Transient K+ channels open and K+ efflux returns TMP to 0mV

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2\. Influx of Ca2+ through L-type Ca2+ channels is electrically balanced by K+ efflux through delayed rectifier K+ channels

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3\. Ca2+ channels close but delayed rectifier K+ channels remain open and return TMP to -90mV

depolarization

first step in muscle excitation

neurogenic muscle

• “beginning in the nerve” - requires nervous input to contract

• stimulated by action of neurons

myogenic muscle

• “beginning in the muscle” - generating contraction independent of nervous input

• contract spontaneously (automaticity of cardiac pacemaker cells)

Neurogenic Muscle (skeletal muscle)

• axon terminals located in sarcolemma region called the motor end plate; has acetylcholine receptors

• once ACh is bound, it opens sarcolemma Na+ channels

• nicotinic ACh receptors initiate a wave of depolarization

• AP passage along the sarcolemma inducing all or none contraction

2 main ways to ensure the entire sarcolemma is depolarized uniformly in space and time

1. through multiple innervations

2. through invaginations of the sarcolemma (t-tubules)

Myogenic Muscle (Cardiac Muscle)

• contract spontaneously without neuron input- heart

• pacemaker cells: heart rhythm, unstable resting membrane potential (cardiomyocytes: contraction)

• unusual ion channel, funny channel or F-channel

  • permeable to both Na+ and K+

  • open upon hyperpolarization, the funny current supplies inward current

  • slow depolarization

pacemaker potential

• F-channel lf- slow depolarization due to Na influx exceeding K efflux

• reaching threshold voltage, voltage-sensitive Ca2+ channels open to initiate the AP

• if pacemaker cells damaged, regular cardiomyocytes have ability to become new pacemakers

• full depolarization due to Ca2+ channels opening

Ca concentration gradient

• more in SR, less in cytosol

• changes with contraction

Calcium regulation and release

• Ca concentration gradient

• dihydropyridine (DHP) receptors (L type Ca channel)

• ryanodine receptors (RyRs)

dihydropyridine (DHP) receptors (L type Ca channel)

• L stands for long-lasting

• located in sarcolemma, voltage-gated

ryanodine receptors (RyRs)

• located in SR

• opening by:

  • skeletal: physical coupling with DHP

  • cardiac: Ca induced Ca release (CICR)

steps of muscle contraction

1. depolarization of sarcolemma

2. myogenic (spontaneous) or neurogenic (motor neuron) with ACh receptors on motor end plate

3. release of Ca

4. Ca binds to troponin C subunit causing conformational change

5. tropomyosin comes off and myosin binding sites are exposed

6. myosin binds actin initiating crossbridge cycle

7. contraction occurs

relaxation

• after depolarization comes repolarization

• removal of Ca from cytosol

steps of relaxation

1. SR Ca2+ ATPase (SERCA) pumps Ca2+ back into SR

2. sarcolemma Ca2+ATPase pumps Ca2+ out of the cell

3. sarcolemma: Na+/Ca2+ exchangers (NCX)

• troponin and TM go back to block myosin-actin interaction

Removal of Ca from cytosol (most to least important)

1. SR Ca2+ ATPase (SERCA)

2. Na+/Ca2+ exchanger (NCX)

3. sarcolemma Ca2+ ATPase

   • both contraction and relaxation need energy

muscle hypertrophy

muscle growth from heavy training

• increases diameter of muscle fibers

• increases number of myofibrils

• increases mitochondria, glycogen reserves

muscle atrophy

lack of muscle activity

* reduces muscle size, tone, and power

physiological hypertrophy of the heart

• stimuli:

  • chronic exercise

  • pregnancy

• results:

  • increase in myocyte length > increase in myocyte width

pathological hypertrophy of the heart

• stimuli

  • hypertension

  • myocardial infarction

  • endocrine disorder

  • etc.

• results:

  • increase in myocyte length < increase in myocyte width

when stored ATP is not enough, back up energy source is _____

phosphocreatine

muscle at rest

ATP from metabolism + creatine - creatine/kinase → ADP + phosphocreatine

working muscle

phosphocreatine + ADP --- creatine/kinase → creatine + ATP