9-2

Muscular System FunctionsBody movementMaintenance of postureRespirationProduction of body heatCommunicationConstriction of organs and vesselsHeart beat

9-3

Properties of MuscleResponsiveness (excitability)

capable of response to chemical signals, stretch or other signals & responding with electrical changes across the plasma membrane

Conductivitylocal electrical change triggers a wave of

excitation that travels along the muscle fiberContractility -- shortens when stimulatedExtensibility -- capable of being stretchedElasticity -- returns to its original resting

length after being stretched

9-4

Muscle Tissue TypesSkeletal

Attached to bonesNuclei multiple and peripherally locatedStriated, Voluntary and involuntary (reflexes)

SmoothWalls of hollow organs, blood vessels, eye,

glands, skinSingle nucleus centrally locatedNot striated, involuntary, gap junctions in

visceral smoothCardiac

HeartSingle nucleus centrally locatedStriations, involuntary, intercalated disks

Skeletal muscle:-

• It has well developed cross striations.

• Doesn’t contract in the absence of nervous stimulation.

• Lacks anatomic & functional connections between individual

muscle fibers.

• It is under voluntary control.

Cardiac muscle also has cross-striations but it contracts

rhythmically in the absence of external innervations owing to

the presence of pace maker cells that discharge

spontaneously.

Smooth m. lacks cross-striations . Found in most hollow

viscera ,it contains pacemakers that discharge irregularly.

Skeletal muscle morphology:-

• Sk.m is made up of muscle fibers that are the “building blocks” of muscular

system . They begin & end in tendons ,arranged in parallel so that force of cont.

is additive.

• Each m. fiber is a single cell multinucleated , long cylindrical & surrounded by

cell memb

• ( sarcolemma), there are no bridges between cells.

• Muscle fibers are made up of myofibrils which are divided into filaments that

made up of contractile proteins.

• The contractile mechanism in sk.m. depends on the proteins: myosin II , actin ,

tropomyosin & troponin. Troponin made up of troponin I, troponinT& troponin C.

• α – actinin binds actin to Z line .titin connects the Z line to the M line providing

structural support & elasticity.

Muscle fibre

General Organization of Skeletal Muscle Tissue

A muscle is anchored at each end by tough connective tissue (tendon) – attached to bone

Muscle comprised of long cylindrical, multinucleated cells called muscle fibers aligned in a parallel fashion

Each muscle fiber is composed of numerous parallel subunits called myofibrils which consist of longitudinally repeated units called sarcomeres (functional unit of striated muscle)

Each sacromere contains 2 kinds of long, thick proteins (called myofilaments) arranged in precise geometric pattern with a Z-disk at each end

Extending from either end of Z-disk are thin filaments consisting largely of protein actin

Thin filaments interdigitate with thick filaments made primarily of protein myosin

Organization

Myofibrils = Contractile Organelles of Myofibrils = Contractile Organelles of MyofiberMyofiber

ActinMyosin

TropomyosinTroponin

Titin Nebulin

ContractileContractile

RegulatoryRegulatory

AccessoryAccessory

Contain 6 types of protein:

9-13

Parts of a Muscle

StriationsDark A bands (regions) alternating with lighter

I bands (regions)anisotrophic (A) and isotropic (I) stand for the

way these regions affect polarized lightA band is thick filament region

lighter, central H band area contains no thin filaments

I band is thin filament regionbisected by Z disc protein

anchoring thick & thinfrom one Z disc to the next is a sarcomere

• The thick filaments are made up of myosin & thin

filaments are made up of actin, tropomyosin, &

troponin.

• The thick fil. are lined up to form A bands whereas

thin fil. Forms I bands.

• Myosin II is made up of 2 heavy chains & 4 light

chains.

• The N-terminal portions of heavy chains & the light

chains combine to form the globular heads which

contain an actin binding site & a catalytic site that

hydrolyzes ATP.

Thick Filaments

Made of 200 to 500 myosin molecules2 entwined golf clubs

Arranged in a bundle with heads directed outward in a spiral array around the bundled tails, heads found on each end with central area a bare zone with no heads

•The thin filaments are made up of two

chains of actin that form a long double

helix.

•Tropomyosin molecules are long

filaments , located in the groove between

the two chains in the actin.

•Each thin filament contains 300-400 actin

molecules & 40-60 tropomyosin molecules.

Troponin molecules are small globular units located at intervals along the tropomyosin molecules. Troponin T binds the other troponin components to tropomyosin. Troponin I inhibits the interaction of myosin with actin. Troponin C contains the binding sites for the Ca++ that initiates contraction.

9-23

Structure of Actin and Myosin

Titin and NebulinTitin and Nebulin

TitinTitin: biggest protein known (25,000 : biggest protein known (25,000 aa); aa); elastic!elastic! Stabilizes position of contractile filamentsStabilizes position of contractile filaments Return to relaxed locationReturn to relaxed location

NebulinNebulin: inelastic : inelastic giant proteingiant protein Alignment of A & MAlignment of A & M

Fig 12-6

Sarcotubular system:-

• Made up of T-system & a sarcoplasmic reticulum. The T

system are transverse tubules which are continuous with

memb. of muscle fiber. The space between two layers of

T-system is extension of ECS ( extra cellular space).

• Sarcoplasmic reticulum has enlarged terminal cisterns.

Central T sys. With a cistern of the sarcoplasmic retic.on

either side called triads.

• The function of T-sys. which is continuous with

sarcolemma is rapid transmission of action potential

from cell memb. to all fibrils in muscle. The

sarcoplasmic retic. Is concerned with Ca++ movement &

muscle metabolism.

More Anatomy

Electrical phenomena & ionic fluxes :-

• Resting memb. potential of sk.m. is − 90 mv . a.p. lasts 2- 4

ms. It conducted along m. fibers at about 5 m /s. absolute

refractory period is 1-3 ms.

• Ionic distribution & fluxes:-

• It is similar to nerve cell memb. depol. Is a manifestation of

Na+ influx. repol. manifestation of K+ efflux.

• Contractile responses:-

• m. fiber memb. depol. Starts at motor end plate , the

specialized structure under motor nerve ending . The a.p.

transmitted along m.f. & initiates the contractile response.

Molecular basis of contraction:-

• Sliding of thin filament over thick fil. Will lead to

shortening & cont. of muscle. A band is constant

but Z-lines move closer together until overlap.

• The sliding occurs when myosin heads bond to

actin, bend on rest of myosin molecule then

detach . this cycle is repeated many times . Each

myosin head has an actin-binding site & an ATP –

binding site( an open cleft , when ATP enters it ,it

hydrolyzed & cleft will close.). this will produce

power stroke that moves actin on myosin .

• Each thick fil. has 500 myosin head , each cycle

about 5 times / s. during rapid cont.

• ATP is catalyzed by ATPase activity in heads of

myosin, in contact with actin.

• Depol. Of m.f. which initiates cont. is called

excitation –cont. coupling.

• The a.p transmitted to all fibrils via T- system.

releasing of Ca++ from terminal cisterns of

sarcoplasmic retic. will initiate cont by binding to

troponin C.

9-32

Cross-Bridge Movement

• In resting muscle , troponin I is tightly bound to

actin & tropomyosin covers the sites where myosin

heads bind to actin. Thus the troponin-tropomyosin

complex constitutes a relaxing protein that inhibits

the interaction between actin & myosin .

• When Ca++ released by a.p , binds to troponin C,

the binding of troponin I to actin is weakened ,

tropomyosin moves laterally, uncovers binding sites

for myosin heads. ATP then split & contraction

occur.

• 7 myosin binding sites are uncovered for

each molecule of troponin that binds a

Ca++ ion.

• After releasing Ca++ , the sarcoplasmic

retic. reaccumulate it by actively

transporting it into longitudinal portion

of reticulum by Ca++-Mg++ ATPase

pump, then Ca++ diffuses to terminal

cisterns ,where it is stored for next a.p.

• Once Ca++ conc. has been lowered , muscle

relaxes .ATP provides energy for both cont.&

relax. if transport of Ca++ into retic. is

inhibited ,relax. not occur , even though there

are no a.p. leading to sustained cont. called a

contracture.

.

Binding Site Tropomyosin

Troponin

Myosin

Motor UnitsSkeletal muscle must be stimulated by a nerve

or it will not contract (paralyzed)Cell bodies of somatic motor neurons are in

brainstem or spinal cord Axons of somatic motor neurons are called

somatic motor fiberseach branches, on average, into 200 terminal

branches that supply one muscle fiber eachEach motor neuron and all the muscle fibers it

innervates are called a motor unit

Motor UnitsFine control

small motor units contain as few as 20 muscle fibers per nerve fiber

eye musclesStrength control

gastrocnemius muscle has 1000 fibers per nerve fiber

Neuromuscular JunctionsSynapse is region where nerve fiber makes a

functional contact with its target cell (NMJ)Neurotransmitter released from nerve fiber

causes stimulation of muscle cell (acetylcholine)

Components of synapsesynaptic knob is swollen end of nerve fiber

contains vesicles filled with ACh

motor end plate is region of muscle cell surface has ACh receptors which bind ACh released from nerve acetylcholinesterase is enzyme that breaks down ACh &

causes relaxation

schwann cell envelopes & isolates NMJ

Muscle Contraction & RelaxationFour phases involved in this process

excitation where action potentials in the nerve lead to formation of action potentials in muscle fiber

excitation-contraction coupling refers to action potentials on the sarcolemma activate myofilaments

contraction is shortening of muscle fiber or at least formation of tension

relaxation is return of fiber to its resting length

Excitation (steps 1 & 2)

Nerve signal stimulates voltage-gated calcium channels that result in exocytosis of synaptic vesicles containing ACh

Excitation (steps 3 & 4)

Binding of ACh opens Na+ and K+ channels resulting in an end-plate potential (EPP)

Excitation (step 5)

Voltage change in end-plate region (EPP) opens nearby voltage-gated channels in plasma membrane producing an action potential

Excitation-Contraction Coupling(steps 6&7)

Action potential spreading over sarcolemma reaches T tubules -- voltage-gated channels open in T tubules causing calcium gates to open in SR

Excitation-Contraction Coupling(steps 8&9)

Calcium release causes binding of myosin to active sites on actin

Contraction (steps 10 & 11)

Myosin head with an ATP molecule bound to it can form a cross-bridge (myosin ATPase releases the energy allowing the head to move into position)

Contraction (steps 12 & 13)

Power stroke shows myosin head releasing the ADP & phosphate and flexing as it pulls thin filament along -- binding of more ATP releases head from the thin filament

Relaxation (steps 14 & 15)

Stimulation ceases and acetylcholinesterase removes ACh from receptors so stimulation of the muscle cell ceases

Relaxation (step 16)

Active transport pumps calcium back into SR where it binds to calsequestrin

ATP is needed for muscle relaxation as well as muscle contraction

Relaxation (steps 17 & 18)

Loss of calcium from sarcoplasm results in hiding of active sites and cessation of the production or maintenance of tension

Role of Calcium Myosin cross-bridges can bind to actin only when binding sites are available – in resting muscle, myosin binding sites on actin thin filaments are covered by tropomyosin

Tropomyosin moves away from myosin binding sites when Ca2+ binds to troponin

Muscle Contraction SummaryNerve impulse reaches myoneural junction

Acetylcholine is released from motor neuron

Ach binds with receptors in the muscle membrane to allow sodium to enter

Sodium influx will generate an action potential in the sarcolemma

Muscle Contraction ContinuedAction potential travels down T tubule

Sarcoplamic reticulum releases calcium

Calcium binds with troponin to move the troponin, tropomyosin complex

Binding sites in the actin filament are exposed

Muscle Contraction ContinuedMyosin head attach to binding sites and create a power stroke

ATP detaches myosin heads and energizes them for another contaction

When action potentials cease the muscle stop contracting

•The muscle twitch:-• A simple a.p. causes a brief cont. followed by

relaxation. this process called muscle twitch.

Twitch starts 2 ms after a depol. Of memb. the

duration varies with type of muscle. Fast m.f.

( those concerned with fine rapid movement) have

short twitch duration as 7.5 ms. Slow m.f ( those

involved in strong , sustained movements) have

twitch durations up to 100 ms.

Muscle TwitchThreshold is minimum voltage necessary to produce

contractiona single brief stimulus at that voltage produces a quick cycle

of contraction & relaxation called a twitch

Phases of a twitch contraction latent period (2 msec) is delay

between stimulus & onset of twitch

contraction phase is period during which tension develops and shortens

relaxation phase shows a loss of tension & return to resting length

refractory period is period when muscle will not respond to new stimulus

Summation of contractions:-

• The fiber is electrically refractory only during rising &

part of the falling phase of spike potential. at this time

cont beginning by first stimulus, repeated stimulation

before relaxation has occurred will produce additional

cont. added to already present cont. this phenomena

known as summation of contractions. The tension here

is greater than single muscle twitch.

• With repeated stimulation , continuous cont. occur

called complete tetanus, when there is no

relaxation.

• Incomplete tetanus occur when there are periods

of incomplete relaxation . The tension developed

during complete tetanus is 4 times that of single

muscle twitch.

Treppe :-

• When a series stimuli delivered to sk.m , at

frequency just below tetanizing frequency , so there

is an increase in tension until after several cont. a

uniform tension / cont. will developed . this

phenomenon known as treppe( staircase).

9-64

Treppe

Graded responseOccurs in muscle

rested for prolonged period

Each subsequent contraction is stronger than previous until all equal after few stimuli

9-65

Multiple-Wave SummationAs frequency of action

potentials increase, frequency of contraction increases Incomplete tetanus

Muscle fibers partially relax between contraction

Complete tetanus No relaxation between

contractionsMultiple-wave

summation Muscle tension

increases as contraction frequencies increase

Relation between muscle length, tension & velocity of cont:

• Passive tension is measured at a given distance ,then the

muscle is stimulated electrically then total tension is

measured. The difference between both is active tension .

• The length of muscle which the active tension is max, is called

resting length.

• The reaction between length- tension in sk.m. is due to sliding

filament ,and cross –linkage between actin & myosin molecules.

• When muscle is stretched the overlap is reduced . when

muscle is shorter than resting length , the thin filaments

overlap & cross-linkage also reduces.

9-67

Muscle Length and Tension

9-68

Types of Muscle ContractionsIsometric: No change in length but

tension increasesPostural muscles of body

Isotonic: Change in length but tension constantConcentric: Overcomes opposing resistance

and muscle shortensEccentric: Tension maintained but muscle

lengthens

Muscle tone: Constant tension by muscles for long periods of time

Isometric & Isotonic Contractions

9-70

Slow and Fast FibersSlow-twitch or high-oxidative

Contract more slowly, smaller in diameter, better blood supply, more mitochondria, more fatigue-resistant than fast-twitch

Fast-twitch or low-oxidativeRespond rapidly to nervous stimulation,

contain myosin to break down ATP more rapidly, less blood supply, fewer and smaller mitochondria than slow-twitch

Distribution of fast-twitch and slow twitchMost muscles have both but varies for each

muscle

Muscle Fiber Classification

Oxidative only

Oxidative or glycolytic

Energy sources & metabolism:-

• m. cont requires energy & muscle is called a “ machine” converting

chemical energy into mechanical work . source of energy is energy –

rich organic phosphate derivatives in muscle.

Phosphorylcreatine:-

• ATP is resynthesized from ADP by addition of a phosphate group .

this reaction requires energy which supplied by break down of

glucose to CO2 & H2O . but there is another compound called

Phosphorylcreatine which is the source of energy of muscle cont.

Carbohydrate & lipid breakdown:-

• At rest & light exercise muscle utilize free fatty acids for energy source but

if intensity of exercise increases lipids alone cannot supply energy , so

utilization of CHO will be predominant source for energy.

• Glucose in bd stream enters cells, when after several chemical reactions

become pyruvate . another source is glycogen which is present in liver &

sk.m. when O2 present pyruvate enters citric acid cycle & end product is

sufficient energy to form large quantities of ATP from ADP this process

called aerobic glycolysis.

• If O2 is insufficient pyruvate doesn’t enter citric acid cycle but reduced to

lactate with net result of much small amount of ATP this process is called

anaerobic glycolysis.

The oxygen debt mechanism:-

• During m. exercise , the m. bd. Vessels dilate , blood flow is

↑ & O2 supply ↑ up to a point the ↑ in O2 consumption is

proportionate to energy expended until it reaches a stage

that aerobic pathway for production of ATP is not enough ,

so that anaerobic pathway will start by breakdown of

glucose to lactate.

• Use of anaerobic pathway is self-limiting because lactate

accumulate in muscle leading to decline in PH.

• After a period of exertion is over, extra O2 is consumed to remove

lactate ,replenish ATP , Phosphorylcreatine stores & small amount of O2

that come from myoglobin. This extra O2 consumption called oxygen

debt

FatigueFatigue is progressive weakness & loss of

contractility from prolonged useCauses

ATP synthesis declines as glycogen is consumedATP shortage causes sodium-potassium pumps to

fail to maintain membrane potential & excitabilitylactic acid lowers pH of sarcoplasm inhibiting

enzyme functionaccumulation of extracellular K+ lowers the

membrane potential & excitabilitymotor nerve fibers use up their acetylcholine

Cardiac muscle Morphology :-

• The striations in cardiac m. are similar to those in

sk.m there are large no. of mitochondria .Z-lines

are present .m.fibers branch & interdigitate , the

end of one m.fiber abuts on another through an

extensive series of folds. these areas occur at Z-

line called intercalated disks. They provide a

strong union between fibers ,that contractile unit

can be transmitted along its axis to the next.

• The cell membs of adjacent fibers fuse forming

gap junctions. These junctions provide low-

resistance bridges for:-

• 1)spread of excitation from one fiber to another .

• 2) they permit cardiac m. to function as if were a

syncytium.

• The T-system in cardiac m. is located at the Z-lines

. like sk.m cardiac m. contains myosin, actin,

tropomyosin & troponin. It also contains

Dystrophin.

Electrical properties:-

Resting memb. & action potentials:-

• Resting memb. of cardiac.m. is about – 90mv.

Stimulation produces a propagated a.p., then

depol. Proceeds rapidly , an overshoot is present,

but it is followed by a plateau before the memb.

potential returns to the baseline. Depol. Lasts

2ms. But plateau & repol lasts 200ms. The

extracellular recording include a spike & a later

wave that resemble QRS complex & T wave of

ECG.

• Changes in external K+ conc. affect the resting

memb. potential, whereas changes in external Na+

conc. affect the magnitude of a.p.

• The initial rapid depol. & overshoot ( phase 0 ) are

due to opening of voltage – gated Na+ channels.

• The initial rapid repol. (phase 1) is due to closure of

Na+ channels .the prolonged plateau ( phase 2 ) is due

to slower but prolonged opening of voltage – gated Ca+

+ channels. Final repol.( phase 3) is due to closure of

Ca++ channels & K+ efflux. This restores the resting

potential ( phase 4).

• The fast Na+ channel in cardiac m. has two gates,

an outer gate that opens at the start of depol. at a

memb. potential of –70 to-80 mv .and an inner

gate that then closes and precludes further influx

until a.p is over(Na+ inactivation)

• The the slow Ca++ channel is activated at a

memb. potential of -30 to -40 mv . there are at

least 8 kinds of K+ channel in the heart. in cardiac

m. the repol. time decreases at rate of 75 b/mi.

( a.p. is 0.25 sec), but at rate of 200 b/min.

( 0.15sec.)

• Mechanical properties:- contractile response:-• It begins just after start of depol.& lasts 1.5

times as long as a.p.

• The role of Ca++ is similar to sk.m. however it is the influx of extracellular Ca++ that is triggered by activation of dihydropyridine channels in the T-sys rather than depol by stored Ca++ from the sarcoplasmic reticulum.

During phase 0-2 and about half phase 3 until a.p. reaches approximately -50 mv during repol , cardiac m. cannot be excited again i.e. it is in its absolute refractory period.it remains refractory until phase 4. therefore , tetanus of sk.m cannot occur. Tetanization of cardiac m. is lethal

•Isoforms:-• Cardiac muscle is slow and has low ATPase

activity. Its fibers dependent on oxidative metabolism, needs continuous O2 supply.

• The human heart contains α and β MHC both in atria, but α is more. Whereas only β isoforms is found in ventricles.

• Correlation between m. fiber length & tension :-

• It is similar to Sk.m. there is a resting length at which the tension developed is maximal.

• In the body the initial length of the fibers is determined by degree of diastolic filling of heart & pressure in ventricle is proportionate to total tension develop

• ( starlings law of the heart ).

• .

• Force of cont. of cardiac m. are ↑ by catecholamines without ↑ in length and it is mediated through β1 adrenergic receptors & c- AMP . it is called positively inotropic effect of catecholamines

• heart also contains β2 –adrenergic receptors which act through c- AMP and it is more in atria.

• Digitalis glycosides ↑ cardiac cont. by inhibiting Na+ -K+ ATPase in cell memb. of m.fibers . the resultant ↑ in intracellular Na+ & ↓ Na+ gradient across cell memb.↓ Na+ influx & Ca++ efflux through Na+ -Ca++ exchange antiport in the cell memb. so ↑ intracellular Ca++ which ↑ strength of cont. of cardiac m.

Metabolism:-• Under basal conditions 35% of caloric needs of

human heart are provided by CHO, 5% ketones & a.a & 60 % by fat.

• Pace maker tissue:-• The heart continues to beat after all nerves to it

are sectioned. It is due to presence of specialized pacemaker tissue that can initiate repetitive a.p. the pace maker tissue makes up the conduction system that spread impulses through out heart. They have unstable memb. potential that slowly decreases after each impulse until reaches firing level.

Smooth muscle morphology:-Fusiform cells with one nucleus

30 to 200 microns long & 5 to 10 microns wide

• 1) S.m lacks cross striations.• 2) Actin & myosin II are present & slide on each other but not arranged in regular arrays.

• 3) Instead of Z- lines there are dense bodies in cytoplasm & attached to cell memb. bound by α- actinin to actin filaments.• 4) Troponin is absent.• 5) Sarcoplasmic reticulum is poorly developed.• 6) Contain few mitochondria and depends on glycolysis

for their metabolic needs.

Types

Divided into :-• 1- visceral s.m (single unit) :-

• as in intestine , uterus , ureters .they has low –

resistance bridges & functions in a syncytial

fashion. The bridges like in cardiac m. form gap-

junction.• 2- multi –unit s.m :- • made up of individual units without

interconnecting bridges. It is found in iris of the eye , in which fine graded cont. occur. It is not under voluntary control, but has many functional similarities to sk. M.

Types of Smooth Muscle

Multiunit smooth musclein largest arteries, iris, pulmonary

air passages, arrector pili musclesterminal nerve branches synapse on

individual myocytes in a motor unitindependent contraction

Single-unit smooth musclein most blood vessels & viscera as

circular & longitudinal muscle layerselectrically coupled by gap junctionslarge number of cells contract as a unit

Stimulation of Smooth Muscle

Involuntary & contracts without nerve stimulationhormones, CO2, low pH, stretch, O2 deficiencypacemaker cells in GI tract are autorhythmic

Autonomic nerve fibers have beadlike swellings called varicosities containing synaptic vesiclesstimulates multiple myocytes at diffuse junctions

• Visceral s.m :- • electrical & mechanical activity:-• Visceral s.m has unstable memb. potential. it

shows continuous irregular cont. independent of nerve supply. This maintains partial cont. called tonus or tone. The memb. potential is about -50 mv.

• There are sin- wave like fluctuations, spikes duration 50 ms. the spikes may occur on rising or falling phases of the sine wave.

• There are pacemaker potentials but generated in multiple foci .the excitation –cont. coupling is very slow the.m. starts to cont. about 200ms after start of spike & 150 ms after spike is over. Peak cont. reaches 500 ms after spike.

Molecular basis for cont.:-

• Ca++ involved in initiation of cont. of s.m. like in

sk.m but visceral s.m. has poorly developed

sarcoplasmic reticulum, so intracellular Ca++ is

due to Ca++ influx from ECF via voltage gated

Ca++ channels.

• Myosin must be phosphorylated for activation of

myosin ATPase which is not necessary in sk.m.

• In s.m Ca++ binds to calmodulin & resulting

complex activates calmodulin- dependent myosin

light chain kinase. this enzyme catalyzes

phosphorylation of light chain & myosin ATPase

will activate , actin slides on myosin & cont.

occur, but in sk.m & cardiac m cont. is triggered

by binding of Ca++ to troponin C.

• Myosin dephosphorylated by phosphatase in the

cell, but this will not lead to relaxation of s.m.

instead s.m. has a latch bridge mechanism by

which dephosphorylated myosin cross-bridges

remain attached to actin for some time after the

cytoplasmic Ca++ conc. falls .this produces

sustained cont. which is important in vascular s.m.

relaxation of s.m. occur when there is final

dissociation of Ca++ -calmodulin complex.

Stimulation • Visceral s.m. contracts when stretched in the

absence of extrinsic innervation, Stretch will lead to ↓ in memb. p , ↑ in frequencies of spikes & ↑ in tone.

• Adding of E or NE to preparation of intestinal s.m . memb. p become larger, spike ↓ in frequency& muscle relaxes. NE exerts both β & α action on s.m. β action ↓ m. tension through c-AMP ( binding intracellular Ca++) . The α action is inhibition of cont. by ↑ Ca++ efflux from muscle cell.

• Ach has opposite effect of E. Ach ↓ memb. p. , spikes become more frequent. Muscles become more active. The effect of Ach through phospholipase C& IP3 which ↑ intracellular Ca++ conc.

Function of the nerve supply to s.m

• Mammals visceral m. has dual nerve supply from two divisions of autonomic nervous system.

• Estrogen ↓the memb. p. of uterine s.m. progesterone ↑ memb. p. & inhibits the electrical & contractile activity of uterine m.

• Relation of length to tension:-• Plasticity:-

• If a piece of visceral s.m is stretched , first it ↑ tension however if s.m continue in stretching tension gradually ↓ .this is called plasticity of s.m.

•Multi- unit s.m :-• Unlike visceral s.m multi unit s.m is • 1) nonsyncytial & cont do not spread widely

through it. because of this cont. multi- unit is more fine & localized than those of visceral s.m.

• 2) Like visceral multi-unit s.m is very sensitive to chemical mediators:- NE causes repeated firing of muscle after a single stimulus leading to an irregular tetanus rather than a single twitch.

• The twitch cont of muscle-unit is like sk.m. except that its duration is 10 times as long.