Membrane Potential 1. Resting membrane potential (RMP): 2. Action Potential (AP):

Resting Membrane Potential (RMP)

• It is the potential difference across the cell membrane.

• If an electrode of a voltmeter is introduced inside the cell and the other electrode is located just outside the cell membrane. The electrical current in the voltmeter will shows a reading of about -70mV for most of the body cells during rest condition

Factors which maintain the RMP are:

1. Uneven distribution of electrolytes across cell membrane. Sodium ions

(Na⁺) are in high concentration outside the cell, while it concentration is low inside the cell. Potassium ions(K⁺) inside the cell is high , while it is low outside the cell .

2. K⁺ move outside the cell which is more than the Na⁺ that move inside the cell. This will create negative charges inside the cell and positive charges outside.

3. Sodium-Potassium pump. It uses energy (ATP), to move three sodium ions from inside to outside of the cell, and it will moves two potassium ions from out side towards inside of the cell, against concentration gradient.

Normally, both Na⁺ and K⁺ will try to move across the cell membrane through pores due to the concentration difference across the cell membrane. If this process continue, it will cause equalization in the concentration of Na⁺ and K⁺ across the membrane, but Na⁺-K⁺ pump prevents this to be occurred. Also by pumping Na⁺ out of the cell, this mechanism will prevents swelling and destruction of the cells, i.e. it keeps the normal volume of the cells.

4. The presence of a big negative molecules inside the cell, as proteins, phosphate , and sulphate which cannot move outside the cell.

Action Potential (AP)

• It is a rapid electrical change in the membrane potential which occurs after stimulation of the cell, followed by a return to the resting membrane potential. The stimulus is either electrical, chemical, or mechanical.

• The size and shape of the action potentials differ considerably from one excitable tissue to an other. An action potential is propagated with the same shape and size along the whole length of a nerve axon or muscle cell

Generation of action potential • Stimulation of the cell, will open the Na⁺

channels, therefore, sodium ions will move rapidly inside the cell causing depolarization.

Then, it will be followed by movement of potassium ions outside the cell through

potassium channels causing repolarisation.

• Stimuli that cause electrical change inside the cell reaching the threshold level (about-55mV) will create action potential. While sub-threshold stimuli will not cause AP.

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Muscle Tissue

• Alternating contraction and relaxation of cells

• Chemical energy changed into mechanical energy

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Properties of Muscle Tissue • Excitability

– responds to chemical messengers (neurotransmitters) released from nerve cells

• Contractility – can shorten and generate force

• Extensibility – can be stretched without damaging the tissue

• Elasticity – can return to original shape after being stretched

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3 Types of Muscle Tissue • Skeletal muscle

– attaches to bone, skin or fascia – is striated with light & dark bands visible with

the microscope – contraction & relaxation is under voluntary

control

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3 Types of Muscle Tissue

• Cardiac muscle – is striated in appearance – is controlled by autonomic nervous system – shows autorhythmicity because of intrinsic

pacemaker

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3 Types of Muscle Tissue • Smooth muscle

– forms erector pili muscles attached to hair follicles in skin

– forms the muscle tunics in the walls of hollow organs

– shows a nonstriated appearance – is involuntary

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Functions of Muscle Tissue • Producing body movements • Stabilizing body positions • Regulating organ volumes

– bands of circularly arranged smooth muscle are sphincters

• Movement of substances within the body – blood, lymph, urine, air, food and fluids, sperm

• Producing heat Contractions and relaxation of skeletal muscle

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Skeletal Muscle -- Connective Tissue • Superficial fascia is loose connective tissue & fat

underlying the skin • Deep fascia: dense irregular connective tissue

around muscle • Connective tissue components of the muscle include

– epimysium: surrounds the whole muscle – perimysium: surrounds bundles (fascicles) of 10-

100 muscle fibers – endomysium: separates individual muscle cells

• All of these connective tissue layers extend beyond the muscle belly to form the tendon

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Connective Tissue Components

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Nerve and Blood Supply • Each skeletal muscle is supplied by a nerve, an

artery, and two veins • Each motor neuron supplies multiple muscle fibers

at the neuromuscular junction • Each muscle cell is supplied by one motor neuron

terminal branch and is in contact with one or two capillaries – nerve fibers & capillaries are found in the

endomysium between individual cells

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Thick & Thin Myofilaments

• Supporting proteins (M line, titin and Z disc help anchor the thick and thin filaments in place)

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Atrophy and Hypertrophy • Atrophy

– wasting away of muscles – caused by disuse (disuse atrophy) or severing of

the nerve supply (denervation atrophy), diet – the transition to connective tissue cannot be

reversed • Hypertrophy

– increase in the diameter of muscle fibers – resulting from very forceful, repetitive muscular

activity and an increase in myofibrils, SR, & mitochondria

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Neuromuscular Junction (NMJ)

• NMJ – end of axon nears the surface of a muscle fiber at its motor end plate region (they remain separated by synaptic cleft or gap)

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Structures of NMJ Region

• Synaptic end bulbs are swellings of axon terminals

• End bulbs contain synaptic vesicles filled with acetylcholine (ACh)

• Motor end plate membrane contains 30 million ACh receptors.

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Pharmacology of the NMJ • Botulinum toxin blocks release of neurotransmitter at

the NMJ so muscle contraction can not occur – bacteria found in improperly canned food – death occurs from paralysis of the diaphragm

• Curare (plant poison from poison arrows) – causes muscle paralysis by blocking the ACh receptors – used to relax muscle during surgery

• Neostigmine (anticholinesterase agent) – blocks removal of ACh from receptors so strengthens

weak muscle contractions of myasthenia gravis – also an antidote for curare after surgery is finished

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Sliding Filament Mechanism Of Contraction • Myosin heads

pull on thin filaments • Thin filaments slide

inward • Z discs come toward

each other • Sarcomeres shorten, the

muscle fiber shortens, & the muscle shortens

• Note: Thick & thin filaments do not change in length

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How Does Contraction Begin? • Nerve impulse reaches an axon terminal;

synaptic vesicles release acetylcholine (ACh) • ACh diffuses to receptors on the sarcolemma • A muscle action potential (membrane

potential change) spreads over sarcolemma and down into the transverse tubules

• SR/Triad releases Ca+2 into the sarcoplasm • This is excitation

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Excitation - Contraction Coupling

• The steps that occur from the muscle action potential reaching the T tubule to contraction of the muscle fiber

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Contraction Cycle - 1 • Repeating sequence of events that cause the

thick & thin filaments to move past each other • 4 steps to contraction cycle

– ATP hydrolyzed by myosin ATPase; ADP and Pi remain attached to myosin binding site; energy is stored in cross-bridge

– Ca+2 released at excitation results in disinihibition of actin; myosin and actin bind

– Power stroke of cross-bridge; ADP and Pi released

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Contraction Cycle - 2 – Fresh ATP binds to myosin ATP-binding site;

myosin detaches from actin • Cycle keeps repeating as long as there is ATP

available & high Ca+2 level near thin filament

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Steps in the Contraction Cycle

• Notice how the myosin head attaches and pulls on the thin filament with the energy released from ATP

The initiation and execution of muscle contraction occur in the following sequential steps. 1. An action potential travels along a motor nerve to its endings on muscle

fibers.

2. At each ending, the nerve secretes a small amount of the neurotransmitter

substance acetylcholine.

3. The acetylcholine acts on a local area of the muscle fiber membrane to

open multiple "acetylcholine-gated" channels through protein molecules

floating in the membrane.

4. Opening of the acetylcholine-gated channels allows large quantities of

sodium ions to diffuse to the interior of the muscle fiber membrane. This

initiates an action potential at the membrane.

5. The action potential travels along the muscle fiber membrane in the same way that action potentials travel along nerve fiber membranes.

6. The action potential depolarizes the muscle membrane, and much of the action potential electricity flows through the center of the muscle fiber. Here it causes the sarcoplasmic reticulum to release large quantities of calcium ions that have been stored within this reticulum.

7. The calcium ions initiate attractive forces between the actin and myosin filaments, causing them to slide alongside each other, which is the contractile process.

8. After a fraction of a second, the calcium ions are pumped back into the sarcoplasmic reticulum by a Ca++ membrane pump, and they remain stored in the reticulum until a new muscle action potential comes along; this removal of calcium ions from the myofibrils causes the muscle contraction to cease.

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Relaxation • Acetylcholinesterase (AChE) breaks down ACh

within the synaptic cleft • Muscle action potential ceases • Active transport pumps Ca2+ back into storage in the

lateral sacs • Calcium-binding protein (calsequestrin) helps hold

Ca+2 in SR (Ca+2 concentration 10,000 times higher than in cytosol)

• Tropomyosin-troponin complex recovers binding site on the actin

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Rigor Mortis • Rigor mortis is a state of muscular rigidity

that begins 3-4 hours after death and lasts about 24 hours

• After death, Ca+2 ions leak out of the SR and allow myosin heads to bind to actin

• Since ATP synthesis has ceased, cross bridges cannot detach from actin until proteolytic enzymes begin to digest the decomposing cells

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The Motor Unit

• Motor unit: one somatic motor neuron & all the skeletal muscle cells (fibers) it stimulates – One nerve cell supplies on average 150 muscle cells

that all contract in unison. • Total strength of a contraction depends on how many

motor units are activated & how large the motor unit is

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Twitch Contraction

• Brief contraction of all fibers in a motor unit in response to – single action potential in its motor neuron

• Myogram: graph of a twitch contraction – the action potential lasts 1-2 msec – the twitch contraction lasts from 20 to 200 msec

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Parts of a Twitch Contraction • Latent Period – 2 msec

– Ca+2 is being released from SR • Contraction Period

– 10 to 100 msec – filaments slide past each other

• Relaxation Period – 10 to 100 msec – active transport of Ca+2 into SR

• Refractory Period – muscle cannot respond

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Wave Summation • If second stimulation applied after the refractory period but

before complete muscle relaxation—second contraction is stronger than first

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Complete and Incomplete Tetanus

• Unfused/incomplete tetanus – if stimulate at 20-30 times/second, there will be only partial

relaxation between stimuli • Fused/complete tetanus

– if stimulate at 80-100 times/second, a sustained contraction with no relaxation between stimuli will result

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Explanation of Summation & Tetanus • Wave summation & both types of tetanus

result from Ca+2 remaining in the sarcoplasm

• Force of 2nd contraction is easily added to the first, because the elastic elements remain partially contracted and do not delay the beginning of the next contraction

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Motor Unit Recruitment • Motor units in a whole muscle fire asynchronously

– some fibers are active others are relaxed – delays muscle fatigue so contraction can be

sustained • Produces smooth muscular contraction

– not a series of jerky movements • Precise movements require smaller contractions

– motor units must be smaller (fewer fibers/nerve) • Large motor units are active when large tension is

needed

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Muscle Fatigue • Inability to contract after prolonged activity

– central fatigue is feeling of tiredness and a desire to stop (protective mechanism)

– depletion of creatine phosphate – decline of Ca+2 within the sarcoplasm

• Factors that contribute to muscle fatigue – insufficient oxygen or glycogen – buildup of lactic acid and ADP – insufficient release of acetylcholine from

motor neurons

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Isotonic and Isometric Contraction

• Concentric (isotonic) contraction: a load is moved • Eccentric (isotonic) contraction • Isometric contraction: no movement occurs

– tension is generated without muscle shortening – maintaining posture & supporting objects in a fixed position

Frogs Skeletal Muscle (Simple Muscle Twitch)

Effect of temp on SMT

Summation of skeletal muscle contraction(increase intensity of stimulation)

SMT-Thresh(0.5) (3) volts

5 volts 8 volts(max)

Summation of skeletal muscle contraction(increase frequency of

stimulation) 5 pps 6.5 pps

10 pps 20 pps

Muscle Fatigue (indirect – direct st)

Muscle Fatigue (direct–indirect st)