PHYSIOLOGY OF NERVE AND MUSCLE CELLS, NEUROMUSCULAR JUNCTION

AND AUTONOMIC NRVOUS SYSTEM:

BY: ASSISTANT PROFESSOR

DR. FARAH NABIL ABBAS

LECTURE 14

O B J E C T I V E S : AT THE END OF THE LECTURE YOU SHOULD BE ABLE TO

•Quick revision of anatomic characteristics of smooth muscles.

•Explain the terms unitary and (multiunit) smooth muscle and differentiate each type.

•Comparison between the electrical properties of the smooth Muscle from the skeletal muscle.

•Understand the molecular basis of contraction of the smooth muscle as compared to the cardiac and skeletal muscle.

•Illustrate latch bridge and plasticity in th esmooth muscle.

Characteristics

• Lack striation

• Lack sarcomeres

• Found in walls of hollow organs and supports visceral function

• Have poorly developed sarcoplasmic reticulum and lack T tubules.

• Lack troponin and instead they have calmodulin

• Slowly contracting muscles

THE SMOOTH MUSCLE:

Characteristics • Can produce more force than some skeletal

muscle and more prolonged contractions with less energy

• Contain less number of mitochondria.

• Actin and myosin grouped into bundles tie in dense bodies

• Function somewhat independently of the NS

• All innervated by neurons of the autonomic NS

THE SMOOTH MUSCLE:

Actin and Myosin Organization

THE SMOOTH MUSCLE:

Characteristics • Contains three filament types a) Thin (Actin): tie to dense

bodies similar to Z lines b) Thick (myosin): much larger

than in skeletal c) Intermediate: non

contractile fibers •These filaments are not

arranged in a regular pattern as in striated muscle,

•as a result smooth muscle can operate over a broader range of stretch.

THE SMOOTH MUSCLE:

Smooth Muscle Filaments

• Smooth muscle is distinguished anatomically from other muscles because it lacks visible cross-striations.

• That is although actin and myosin are present and slide on each other, they are not arranged in regular arrays as in skeletal or cardiac muscle. Smooth muscle also contains tropomyosin, but not troponin.

• Large numbers of actin filaments are attached to the so-called “dense bodies”, with myosin filaments scattered among the actin filaments.

Anatomic Consideration:

•There is a sarcoplasmic reticulum, but it is poorly developed.

• In general, smooth muscles contain few mitochondria and depend to a large extent on anaerobic glycolysis for their metabolic needs.

• In general, smooth muscle can be divided into unitary (visceral or single-unit) and multiunit smooth muscle.

Anatomic Consideration:

•The term “unitary” is confusing because it

does not mean single fibers; but a mass of hundreds to thousands of smooth muscle fibers

that contract together as a single unit (syncytium).

•Unitary smooth muscle occurs in large sheets and is found primarily in the walls of hollow viscera; including the musculature of

the intestine, bile ducts, ureters, uterus and many

blood vessels.

•The cell membranes of these muscle fibers are adherent to one another at multiple points so that force generated at one muscle fiber can be transmitted to the next.

THE SMOOTH MUSCLE: Un i ta ry (V i s cera l ) smoo th musc le :

•It has low-resistance bridges where the membranes of two adjacent cells fuse to form (gab junctions)

•through which ions can flow freely between individual muscle cells.

•Therefore, it functions in a syncytial fashion, as in cardiac muscle.

•Visceral smooth muscle is not under voluntary control, and a major share of its control is exerted by non-nervous stimuli (hormonal, chemical and stretch).

THE SMOOTH MUSCLE: Un i ta ry (V i s cera l ) smoo th musc le :

•Multiunit smooth muscle is made up of individual, discrete muscle units without interconnecting bridges.

•Each fiber contracts independently of the others and is often innervated by a single nerve ending; yet, it is not under voluntary control.

•Another important characteristic of these muscles is that their control is exerted mainly by nerve signals,

•found in structures in which fine graded contractions occur, e.g the ciliary muscle and iris muscle of the eye, as well as the piloerector muscles.

THE SMOOTH MUSCLE: Mul t iun i t smoo th musc le :

• It is characterized by the instability of its

membrane potential. Thus, its membrane potential has no “resting” value;

• yet, in periods between increased and decreased activity, it averages (–50 mV).

• Superimposed on this membrane potential are slow, sine wave-like fluctuations (oscillations) a few mVs in magnitude, e.g visceral smooth muscle of the gut.

• Slow waves themselves are not APs, but can

initiate APs when peak of the negative

wave reaches about (–35 mV), (firing level).

THE SMOOTH MUSCLE: Unitary (Visceral) smooth muscle : Electrical and Mechanical Activity

•APs of the visceral smooth muscles occur in one of the following:

1) spike potentials or

2) APs with plateaus.

•The pacemaker potentials are generated in multiple foci shifting from one place to another

•They are conducted for some distance, controlling the rhythmical contractions (peristalsis) of the gut.

THE SMOOTH MUSCLE: Unitary (Visceral) smooth muscle : Electrical and Mechanical Activity

• Typical spike potentials may occur on the rising or falling phases of the oscillations.

• Spike potentials are of short duration (10–50 ms) and can be elicited by

• electrical stimulation,

• by hormones,

• by transmitter substances from nerve fibers,

• by stretch or

• spontaneously generated in the muscle fiber itself.

• On the other hand, APs have a prolonged plateau phase just like in cardiac muscle.

THE SMOOTH MUSCLE: Unitary (Visceral) smooth muscle : Electrical and Mechanical Activity

• In unitary smooth muscle, the repolarization is delayed for several hundred milliseconds to 1 second.

• The importance of the plateau is that it accounts for the prolonged contractions in some types of smooth muscles like the ureter, the uterus under some conditions and vascular smooth muscle.

• As a result, visceral smooth muscle shows a continuous maintained state of irregular partial contractions that are independent of its nerve supply and are called tonus or tone of the muscle.

THE SMOOTH MUSCLE: Unitary (Visceral) smooth muscle : Electrical and Mechanical Activity

• Visceral smooth muscle starts to contract about (200 ms) after the start of the spike potential, and the peak contraction about (500 ms) after the spike.

• Thus, the excitation-contraction coupling is a very slow process.

Remember; in skeletal and cardiac muscle, time from initial depolarization to initiation of contraction is <10 ms.

• Ca+2 is involved in the initiation of contraction of the smooth muscle.

• The myosin in the smooth muscle must be phosphorylated for the activation of myosin ATPase activity that will cause the power stroke.

THE SMOOTH MUSCLE: Unitary (Visceral) smooth muscle : Molecular Basis of Contraction:

• Being a slow muscle, the time that the cross-bridges remain attached to actin filaments is greatly increased,

• causing a greater maximum force of contraction.

• A possible reason for the slow cycling is because of far less myosin ATPase activity

than in skeletal muscles.

• Instead, Ca+2 binds to calmodulin protein and the resulting Ca+2-calmodulin complex activates the enzyme myosin kinase

• This enzyme catalyzes the phosphorylation and activation of myosin ATPase, causing contraction.

THE SMOOTH MUSCLE: Unitary (Visceral) smooth muscle : Molecular Basis of Contraction:

• Relaxation of visceral smooth muscle occurs when Ca+2 ion concentration falls below a critical level, causing dissociation of Ca+2-calmodulin complex.

• Contractile processes are reversed, except for the phosphorylation of the myosin head which requires another enzyme, myosin phosphatase.

• This enzyme splits the phosphate from myosin, then cross-bridge cycling stops and contraction ceases.

THE SMOOTH MUSCLE: Unitary (Visceral) smooth muscle : Molecular Basis of Contraction:

•Here, myosin cross-bridges remain attached to actin for sometime after decreased Ca+2 concentration. This mechanism produces sustained contraction with little expenditure of energy.

•Once developed full contraction, the amount of excitation usually can be reduced to far less the initial level and the energy consumed to maintain contraction is often very small.

•The importance of the latch bridge mechanism is that it can maintain prolonged tonic contractions for hours or days.

•Especially important in vascular smooth muscle to maintain the blood pressure. In addition to organs such as the intestine, urinary bladder and gallbladder often maintain tonic muscle contraction almost indefinitely.

L a t c h B r i d g e M e c h a n i s m :

•It is the variability of the tension the smooth muscle exerts at any given length.

•If a piece of visceral smooth muscle is stretched, it first exerts increased tension, however, the tension gradually decreased after a while.

•It is, therefore, impossible to correlate length to developed tension accurately, and no resting length can be assigned.

•The consequences of plasticity can be demonstrated in intact human urinary bladder.

R e l a t i o n o f L e n g t h t o Te n s i o n

P l a s t i c i t y

•Visceral smooth muscle contracts when stretched in the absence of any extrinsic innervation: There will be

- a decline in the membrane potential (less negative).

- an increase in the frequency of the spikes.

- a general increase in muscle tone.

• If catecholamines (epinephrine and norepinephrine) added to a preparation of intestinal smooth muscle:

- the membrane potential usually becomes larger (more negative).

- the spikes decrease in frequency.

- the muscle relaxes (decreased tone).

•Normally, stimulation of noradrenergic nerves to the intestine inhibits intestinal contraction in vivo.

THE SMOOTH MUSCLE: S t i m u l a t i o n :

• Acetylcholine has an effect opposite to that of norepinephrine on the membrane potential and the contractile activity of intestinal smooth muscle:

- the membrane potential decreases (more positive).

- the spikes become more frequent.

- the muscle becomes more active with an increase in tonic tension and the number of rhythmic contractions.

• In the intact animal (in vivo), stimulation of cholinergic nerves causes excitatory potentials and increased intestinal contractions.

• In vitro, similar effects are produced by cold and stretch.

THE SMOOTH MUSCLE: S t i m u l a t i o n :