Contractile mechanism of smooth muscle

Physical Basis for Smooth Muscle Contraction

• No striated arrangement of actin and myosin filaments
• actin filaments attached to so-called dense bodies – Some attached to the cell membrane –
Others dispersed inside the cell. – Some of the membrane dense bodies of adjacent cells
bonded together by intercellular protein bridges.
• the force of contraction is transmitted from one cell to the next through these bonds • myosin
filaments: Interspersed among the actin filaments
– diameter: more than twice that of the actin filaments.
– Number: 5 to 10 times as many actin filaments as myosin filaments
• Arrangement: – actin filaments radiating from two dense bodies; the ends of these filaments
overlap a myosin filament located midway between the dense bodies.
• This contractile unit is similar to the contractile unit of skeletal muscle, but without the
regularity of the skeletal muscle structure – (dense bodies of smooth muscle serve the same
role as the Z discs in skeletal muscle)
• smooth muscle cells can contract as much as 80 per cent of their length ( less than 30 per cent
in skeletal muscle)
Chemical Basis for Smooth Muscle Contraction

• actin and myosin filaments

• chemical characteristics similar to those of the actin and myosin filaments in skeletal muscle

• no troponin complex

• actin and myosin filaments interact with each other in much the same way

• contractile process is activated by calcium ions, and ATP is degraded to ADP to provide the
energy for contraction.

• major differences – physical organization – excitation-contraction coupling – control of the

contractile process by calcium ions – duration of contraction – amount of energy required for
contraction. 

 Comparison of Smooth Muscle Contraction and Skeletal Muscle Contraction

• most smooth muscle contraction is prolonged tonic contraction, sometimes lasting hours or even
days – most skeletal muscles contract and relax rapidly

• physical and the chemical characteristics of smooth muscle versus skeletal muscle contraction are
different 

Differences between Smooth Muscle Contraction and Skeletal Muscle Contraction

1. Slow Cycling of the Myosin Cross-Bridges

2. Energy Required to Sustain Smooth Muscle Contraction
3. Slowness of Onset of Contraction and Relaxation
4. Force of Muscle Contraction
5. "Latch" Mechanism for Prolonged Holding of Contractions of Smooth Muscle
6. Stress-Relaxation of Smooth Muscle

Slow Cycling of the Myosin Cross-Bridges

• (attachment to actin, then release from the actin, and reattachment for the next cycle) – frequency
= 1/10 to 1/300 that in skeletal muscle – fraction of time that the cross-bridges remain attached to
the actin filaments (a major factor that determines the force of contraction):

• greatly increased in smooth muscle – reason :

• cross-bridge heads have far less ATPase activity than in skeletal muscle, so that degradation of the
ATP that energizes the movements of the cross-bridge heads is greatly reduced, with corresponding
slowing of the rate of cycling.

Energy Required to Sustain Smooth Muscle Contraction

• Only 1/10 to 1/300 as much energy is required to sustain the same tension of contraction in smooth
muscle as in skeletal muscle

• Mechanism: – slow attachment and detachment cycling of the cross-bridges

• because only one molecule of ATP is required for each cycle, regardless of its duration. – This
sparsity of energy utilization by smooth muscle is exceedingly important to the overall energy
economy of the body ( tonic muscle contraction)

Slowness of Onset of Contraction and Relaxation of Smooth Muscle Tissue

• total contraction time of 1 to 3 seconds (Range: 0.2 second to 30 seconds)

• (30 times as long as a single contraction of an average skeletal muscle fiber) – Onset of
contraction: 50 to 100 milliseconds after it is excited – Achievement of full contraction: about 0.5
second later – decline in contractile force: in another 1 to 2 seconds

• Mechanism: 1. slowness of attachment and detachment of the cross- bridges with the actin
filaments 2. slower response to calcium ions

Force of Muscle Contraction

• greater than that of skeletal muscle – 4 to 6 kg/cm2 cross-sectional area for smooth muscle – (3 to
4 kilograms for skeletal muscle)

• Despite – few myosin filaments – slow cycling time of the cross-bridges

• Mechanism: – prolonged period of attachment of the myosin cross-bridges to the actin filaments.

 "Latch" Mechanism for Prolonged Holding of Contractions of Smooth Muscle

• Definition: muscle maintains its full force of contraction despite reduced amount of continuing
excitation and lesser energy required for comparable sustained skeletal muscle contraction

• importance: – it can maintain prolonged tonic contraction in smooth muscle for hours with little use
of energy.

• Little continued excitatory signal is required from nerve fibers or hormonal sources. 

1. Stress-Relaxation of Smooth Muscle • important characteristic of smooth muscle, especially

the visceral unitary type of smooth muscle of many hollow organs • Definition: ability to return
to nearly its original force of contraction seconds or minutes after it has been elongated or
shortened. • Example: – change in fluid volume in the urinary bladder • These phenomena
are called – stress-relaxation and reverse stress-relaxation. • importance: – except for short
periods of time, they allow a hollow organ to maintain about the same amount of pressure
inside its lumen despite long-term, large changes in volume.
2. Regulation of Contraction by Calcium Ions • initiating stimulus: – an increase in intracellular
calcium ions • Mechanism of increase in intracellular calcium ions 1. nerve stimulation 2.
hormonal stimulation 3. stretch of the fiber 4. change in the chemical environment of the fiber
– smooth muscle does not contain troponin – different mechanism 

Calmodulin, Myosin Kinase and Phosphorylation of the Myosin Head

• In place of troponin, smooth muscle cells contain a large amount of another regulatory protein
called calmodulin. – similar to troponin BUT different in the manner in which it initiates contraction. –
Calmodulin does this by activating the myosin cross- bridges.

Sequence of events

– The calcium ions bind with calmodulin.

– The calmodulin-calcium combination joins with and activates myosin kinase, a phosphorylating
enzyme.
– One of the light chains of each myosin head, called the regulatory chain, becomes phosphorylated
in response to this myosin kinase.

– when the regulatory chain is phosphorylated, the head has the capability of binding repetitively
with the actin filament and proceeding through the entire cycling process of intermittent "pulls," the
same as occurs for skeletal muscle, thus causing muscle contraction.

Cessation of Contraction-Role of Myosin Phosphatase

• When the calcium ion concentration falls below a critical level, the aforementioned processes
automatically reverse, except for the phosphorylation of the myosin head.

• Reversal of this requires another enzyme, myosin phosphatase, located in the fluids of the smooth
muscle cell, which splits the phosphate from the regulatory light chain. Then the cycling stops and
contraction ceases.

• The time required for relaxation of muscle contraction, therefore, is determined to a great extent by
the amount of active myosin phosphatase in the cell.

Mechanism for Regulation of the Latch Phenomenon

• When the myosin kinase and myosin phosphatase enzymes are both strongly activated, the cycling
frequency of the myosin heads and the velocity of contraction are great.

• Then, as the activation of the enzymes decreases, the cycling frequency decreases, but at the
same time, the deactivation of these enzymes allows the myosin heads to remain attached to the
actin filament for a longer and longer proportion of the cycling period.

• Therefore, the number of heads attached to the actin filament at any given time remains large.

• Because the number of heads attached to the actin determines the static force of contraction,
tension is maintained, or "latched"; yet little energy is used by the muscle, because ATP is not
degraded to ADP except on the rare occasion when a head detaches. 

Nervous and Hormonal Control of Smooth Muscle Contraction

• skeletal muscle fibers are stimulated exclusively by the nervous system

• smooth muscle can be stimulated to contract by multiple types of signals:

1. nervous signals
2. hormonal stimulation
3. stretch of the muscle etc

• reason: – many types of receptor proteins that can initiate the contractile process. – other receptor
proteins inhibit smooth muscle contraction (another difference from skeletal muscle)

Importance of Calcium Channels in Generating the Smooth Muscle Action Potential

• more voltage-gated calcium channels (few voltage- gated sodium channels)

• Therefore, flow of calcium ions to the interior of the fiber is mainly responsible for the action
potential. • calcium channels open many times more slowly than do sodium channels,

• and they also remain open much longer. → prolonged plateau

• calcium performs two tasks at once 1. action potential 2. calcium ions act directly on the smooth
muscle contractile mechanism to cause contraction.

Excitation of Visceral Smooth Muscle by Muscle Stretch

• Mechanism: (1) the normal slow wave potentials (2) decrease in overall negativity of the membrane
potential caused by the stretch itself. • Importance: – when excessively stretched→ contract
automatically and rhythmically.

• Example: – intestine 

1. Factors that Cause Smooth Muscle Contraction Without Action Potentials

(1) local tissue chemical factors and (2) various hormones.
2. Smooth Muscle Contraction in Response to Local Tissue Chemical Factors
1. oxygen
2. carbon dioxide
3. hydrogen ion concentration
4. Adenosine
5. Lactic acid
6. potassium ions
7. calcium ion concentration and
8. body temperature

Effects of Hormones on Smooth Muscle Contraction 1. norepinephrine, 2. Epinephrine, 3.

acetylcholine, 4. angiotensin, 5. endothelin, 6. Vasopressin, 7. Oxytocin, 8. serotonin, and 9.
histamine.
• Receptors: – hormone-gated excitatory receptors – hormone-gated inhibitory receptors 

Mechanisms of Action of Hormones or Local Tissue Factors. • Changes in ion permeabilities

(Na+, K+, Ca++) – Inhibit/ Excite • Changes in intracellular enzyme activity – Inhibit/ Excite –
Second messenger system of receptors

Source of Calcium Ions That Cause Contraction (1) Through the Cell Membrane (2) from the
Sarcoplasmic Reticulum
• sarcoplasmic reticulum is less developed in most smooth muscle • almost all the calcium ions
that cause contraction enter the muscle cell from the extracellular fluid at the time of the action
potential or other stimulus.
• latent period : time required for this diffusion of Ca++ (200 to 300 milliseconds , about 50 times
as great as for skeletal muscle contraction.

 Role of the Smooth Muscle Sarcoplasmic Reticulum.

• release of calcium ions from the skeletal muscle longitudinal sarcoplasmic tubules
• The more extensive the sarcoplasmic reticulum in the smooth muscle fiber, the more rapidly it
contracts.
• the force of contraction of smooth muscle usually is highly dependent on extracellular fluid
calcium ion concentration (as sarcoplasmic reticulum is less developed in most smooth muscle) 

A Calcium Pump Is Required to Cause Smooth Muscle Relaxation

• to pump calcium ions out of the smooth muscle fiber back into 1. extra-cellular fluid, or into 2.
sarcoplasmic reticulum, if it is present.
• This pump is slow-acting in comparison with the fast-acting sarcoplasmic reticulum pump in
skeletal muscle →
• Smooth muscle contraction often lasts longer (for seconds) rather than hundredths to tenths of
a second, as occurs for skeletal muscle.