Physiology of Smooth Muscle

Dr. Shafali Singh

Learning Objectives

• Basic structure,functions and types of smooth muscles

• Excitation contraction coupling in smooth muscles

• Relaxation• Properties of smooth muscle

Smooth muscle

• Muscle lining vessels & hollow organs, such as the gastrointestinal tract, the bladder, and the uterus, the ureters and the bronchioles.

• Sheets of small spindle-shaped (fusiform) cells, connected by special junctions.

• Single nucleus (mononucleate). • Contractile units randomly arranged

Special features of Smooth Muscle• Not striated. • Contractile units randomly arranged• NO Z line ( Instead Dense Bodies present in the cytoplasm & in the cell membrane )• Lots of actin, some myosin• T –Tubule absent, hence triads also absent• Caveoli – Analog of T –Tubule• Sarcoplasmic reticulum is poorly developed• Troponin is absent, instead calmodulin is present

• “Sidepolar” cross bridges Most of the Myosin filaments have arranged so that

the bridges on one side hinge in one direction & those on the other side hinge in the opposite direction that it allows smooth muscle cells to contract as much as 80 per cent of their length

● Contractions have longer duration and less tension

Structure of Smooth Muscle

intermediatefilament

contractileproteins

densebodies

mechanicaljunctions

gap junctions

The fibrillar contractile apparatus● Dense bodies serve as an attachment points for the thin filaments●Intermediate filaments form a cytoskeletal network between them

Smooth Muscle Organisation

Gap junctions assure contraction as “single unit.”

Types of Smooth Muscle

Single unit (most):• Clusters of smooth cells, connected by gap junctions. • Activity in one cell spreads to other cells and acts as a

single functional unit. e.g. gut, uterus, bladder.Multi-unit:

Acts as individual units , no syncytium• e.g. Intrinsic muscles of eye (iris), skin piloerectors,

large blood vessels .

Fewer gap junctions assure independent contraction and more precise control.

Single unit & Multi unit SM - Differences Single unit1. Large sheets2. Low resistance

bridges3. Syncytium4. Seen in: uterus,

urethra, intestine, ureter, urinary bladder

5. Pace maker activity present

Multi unit• Individual units• No bridges

• Non- syncytial• Iris, Ciliary muscles of

the eye, piloerector muscle of skin, blood vessels

• No pace maker activity

Single unit6. Rhythmic contraction

and relaxations are independent of innervation

7.Stretch causes contraction

8.No tetanic contracton

Multi unit• Contractions are

stimulated only by ANS

• Stretch cannot cause contraction

• Irregular tetanic contractions present

Basic steps in contraction of SMDepolarisation of muscle fibres

↓Release of Ca++ from sarcoplasmic reticulum & from ECF

↓Ca++ combines with calmodulin

↓Activation of myosin light chain kinase

↓Phosphorylation of myosin

↓Sliding of actin over myosin

Mechanisms for increasing intracellular Ca

Cross-bridge cycling in smooth muscle

SM in relaxed & contracted state

• Calponin and Caldesmon are other two thin filamentous proteins which in resting state of muscle bind actin and also inhibit myosin ATPase preventing the interaction of actin and myosin.

• Ca2+-calmodulin complex leads to their phosphorylation which in turn releases them from their inhibition.

Relaxation in smooth muscles• Occurs when the intracellular Ca2+ concentration falls.• Mechanisms for fall in intracellular Ca:– Repolarisation of sarcolemmal membrane which closes

voltage gated Ca2+ channels– Direct inhibition of Ca2+ channels on sarcolemma by

ligands such as cGMP– Inhibition of IP3 production and decreased release of Ca2+

from sarcoplasmic reticulum– SERCA pump

• Activation of myosin light chain phosphatase which dephosphorylates myosin light chain leading to inhibition of myosin ATPase.

Relaxation of SMContraction

↓Dephosphorylation of myosin

↓- Relaxation or

- sustained contraction due to latch bridge mechanism

i.e. Prolonged tonic contraction for hours with

little use of energy

Comparison of Smooth Muscle Contractionand Skeletal Muscle Contraction

1. Slow Cycling of the Myosin Cross-Bridges2. Energy Required to Sustain Smooth Muscle

Contraction3. Slowness of Onset of Contraction and

Relaxation of the Total Smooth Muscle Tissue.4. Force of Muscle Contraction.5. “Latch” Mechanism for Prolonged Holding of

Contractions ofSmooth Muscle.

Smooth muscle contracts slowly and efficiently.

Characteristics of smooth muscle contraction

• Slow cycling of myosin cross bridges – less ATPase activity

• Less energy required for sustaining muscle contraction

• Slowness of onset of contraction and relaxation

• Maximum force of contraction is greater• Latch mechanism for prolonged holding

of contraction

Electrical properties of SM

• RMP (In the normal resting state, the intracellular potential isusually about -50 to -60 millivolts,). It is Unstable leading to spontaneous excitation.

• Depolarisation due to the entry of Ca++ mainly and Na+ to a lesser extent.

Repolarisation due to delayed K+ efflux & closure of Ca++ channels.

Action Potentials in Unitary Smooth Muscle

(1) spike potentials or(2) action potentials with plateaus.

Mem

bra

ne p

ote

nti

al (m

V)

-60

-45

0

200 msec

Action potential

K+ efflux

Ca2+ influx

Threshold of VOC’s

Some smooth muscle generates its own (pacemaker potentials/slow waves), e.g.,

intestinal peristalsis

Excitation of Visceral Smooth Muscle by Muscle Stretch

When visceral (unitary) smooth muscle is stretchedsufficiently, spontaneous action potentials usuallyare generated. They result from a combination of(1)the normal slow wave potentials and (2) decrease in overall negativity of the membrane

potential caused by the stretch itself.

Depolarization of Multi-Unit Smooth MuscleWithout Action Potentials

• Normally contract mainly in response to nerve stimuli.• The nerve endings secrete acetylcholine in the case of some

multi-unit smooth muscles and norepinephrine in the case of others.

• In both instances, the transmitter substances cause depolarization of the smooth muscle membrane, and this in turn elicits contraction.

• Action potentials usually do not develop; the reason is that the fibers are too small to generate an action potential.

• Yet, in small smooth muscle cells, even without an action potential, the local depolarization (called the junctional potential) caused by the nerve transmitter substance itself spreads “electrotonically” over the entire fiber and is all that is needed to cause muscle contraction.

Effect of Local Tissue Factors and Hormones to Cause Smooth Muscle Contraction Without Action Potentials

• Smooth Muscle Contraction in Response to Local Tissue Chemical Factors.

• Effects of Hormones on Smooth Muscle Contraction.

1. Lack of oxygen in the local tissues causes smoothmuscle relaxation and, therefore, vasodilatation.2. Excess carbon dioxide causes vasodilatation.3. Increased hydrogen ion concentration causesvasodilatation.Adenosine, lactic acid, increased potassium ions,diminished calcium ion concentration, and

increasedbody temperature can all cause local vasodilatation

Modulation of Smooth Muscle Activity by Neurotransmitters, Hormones, and Local Factors

Mechanisms of Smooth Muscle Excitation or Inhibition by Hormones or Local Tissue Factors

Excitation• Some hormone receptors in

the smooth muscle membrane open sodium or calcium ion channels and depolarize the membrane,

• Sometimes action potentials result,

• Action potentials that are already occurring may be enhanced.

• Depolarization occurs without action potentials, and this depolarization allows calcium ion entry into the cell,

Inhibition• closes the sodium and calcium

channels to prevent entry of these positive ions;

• normally closed potassium channels are opened, allowing positive potassium ions to diffuse out of the cell.

• Both of these actions increase the degree of negativity inside the muscle cell, a state called hyperpolarization, which strongly inhibits muscle contraction.

Smooth muscle that exhibits rhythmical contraction in the absence of external stimuli also necessarily exhibits which of the following?

A) “Slow” voltage-sensitive Ca11 channelsB) Intrinsic pacemaker wave activityC) Higher resting cytosolic Ca11 concentrationD) Hyperpolarized membrane potentialE) Action potentials with “plateaus

Mechanical properties of SM

1. Spontaneous activity seen.2. Maintained state of partial contraction is Tonus or Tone.3. No correlation between electrical & mechanical

events Muscle starts contracting 200msec after the spike –

peak contraction is after 500msec

Mechanical properties of SM– contd.

4. Plasticity• Relationship between initial length of muscle

fiber and tension• Tension is variable at any given length• Studied in Human urinary bladder• Useful in accomodating more blood by

vessels, more food by stomach & more urine by bladder without a rise in pressure.

Smooth and skeletal muscle mechanicalcharacteristics compared.

Modulation of Smooth Muscle Activity by Neurotransmitters, Hormones, and Local Factors

• Hormones & drugs:– Adrenaline & Noradrenaline : Similar to SNS– ACh : Similar to PNS– Atropine : Cause relaxation by blocking

parasympathetics.– Pilocarpine : Similar to Ach– Estrogen and Progesterone on uterus– Oxytocin at the time of labour

• Cold, Stretch & barium ions stimulate contraction.• Hypoxia, hypercapnia, acidosis, K+ cause relaxation

Other factors that influence SM:

Q Which statement below most closely describes the role of calcium ions in the control of smooth muscle contraction?(A) Binding of calcium ions to regulatory proteins on thin filaments removes the inhibition of actin-myosin interaction(B) Binding of calcium ions to regulatory proteins associated with thick filaments, specifically calmodulin, activates the enzymatic activity of myosin molecules(C) Calcium ions serve as a direct inhibitor of the interaction of thick and thin filaments(D) A high concentration of calcium ions in the myofilament space is required to maintain muscle in a relaxed state

Q. Compared with skeletal muscle,smooth muscle(A) Contracts more slowly, but exerts considerably more force(B) Contracts more rapidly, but exerts considerably less force(C) Maintains long-duration contractions economically(D) Exerts considerable force but can do little shortening

Differences between skeletal,smooth and cardiac muscle

• Morpological properties—DistributionStructureSize and shapeSarcoplasmic reticulumSarcotubular systemNerve supplyControl and rhythmicityBlood supply

• Electrical propertiesRMPAPAbsolute refractory period

• Mechanical propertiesMechanical eventsDuration of muscle twitchExcitation contraction couplingAll or none lawLength tension relationshipFatigueEnergy utilization