Stimulation Of Receptors By Various Neurotransmitters Biology Essay

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The contraction of smooth muscle involves the stimulation of receptors by various neurotransmitters. Investigations have been carried out to determine the underlying process, resulting in the development of chemicals and drugs to manipulate the behaviour of the smooth muscle to treat various conditions. The review will look at the principles of smooth muscle structure and function, looking at the types investigations and discoveries.

The muscle in the walls of the hollow organs are made of smooth muscle. The fibres are spindled shape cells, and have a diameter of 5-10mm and are 30-200mm long. There are small amounts of fine connective tissues (endomysium) found between smooth muscle fibres, which contain blood vessels and nerves.

Most of the smooth muscle found in the body are organised into sheets of fibres. In most cases two layers of smooth muscles are present; the longitudinal and circular layers, with their fibres positioned at right angles to each other. The longitudinal layer has muscle fibres which run parallel to the long axis of the organ. The organ dilates and shorten when this layer contracts. The circular layer consists of fibres which travel across the circumference of the organ. The lumen of the organ constricts and the organ itself elongates when this layer contracts.

(Human Anatomy and Physiology 8th Edition, Marieb and Koehn, Pearson)

The alternating action of contraction and relaxation enables the organ to squeeze substances along through a process called peristalsis. Smooth muscle contraction of the bladder, rectum and uterus allows the contents in these organs to be emptied. Smooth muscle contraction also causes constricted breathing in asthmatics and stomach cramps. (Human Anatomy and Physiology 8th Edition, Marieb and Koehn, Pearson)

(Human Anatomy and Physiology 8th Edition, Marieb and Hoehn , Pearson, )

The nerve fibres of smooth muscle are part of the autonomic nervous system and contain varicosities. These swellings release neurotransmitters into the synaptic cleft in the cell area. This junction is called a diffuse junction. (Human Anatomy and Physiology 8th Edition, Marieb and Koehn, Pearson)

The sarcoplasmic reticulum of smooth muscle is less intricate than that of skeletal muscle. Some of the tubules sarcoplasmic reticulum touch the sarcolemma at several points, and this couples the action potential to release calcium from the sarcoplasmic reticulum. The sarcolemma posses caveolae; pouch-like foldings which captures the extracellular fluid containing calcium, bringing it closer to the membrane. (Human Anatomy and Physiology 8th Edition, Marieb and Koehn, Pearson)

Smooth muscle fibres contain thick and thin filaments and contain a different type myosin than that present in skeletal muscle. Thick filaments contain myosin heads along the length of the smooth muscle, which the gripping of actin making it as powerful as skeletal muscle. The thin filaments contain a protein known as calmodulin, which acts as a calcium-binding site, instead of the troponin found in skeletal muscle. Proteins are arranged in criss-cross form, so they spiral along the smooth muscle like the stripes on a barbers pole. As a result the smooth muscle contracts in a twisting way resembling tiny corkscrews. Intermediate filaments are found in the fibres, which resist tension and do not contract. These filaments are attached to cytoplasmic structures called dense bodies, and these act as anchoring points for thin filaments. The intermediate filament/dense body structure forms a strong intracellular cytoskeleton that harnesses the pull of the sliding thin and thick filaments. When the muscle contracts, parts of the sarcolemma between the dense bodies bulge outwards to give a puffed-up appearance. The dense bodies bind the muscle cell to connective fibres outside the cell and to other cells. This transmits the pulling force to other connective tissue, and contributes to the synchronous contraction of most smooth muscle cells. (Human Anatomy and Physiology 8th Edition, Marieb and Koehn, Pearson)

Types of smooth muscle

The structure of smooth muscle differs in different body organs. In terms of:

The arrangement of fibres

The innervation

The level of response

In summary, there are two types of single-unit and multiunit (Human Anatomy and Physiology 8th Edition, Marieb and Koehn, Pearson)

Single-Unit smooth muscle

It is also known as visceral muscle and is the most common. The cells of single-unit smooth muscle are:

Are arranged in opposing (longitudinal and circular) sheets

Are stimulated by the ANS varicosities and display rhythmic spontaneous action potential.

Respond to different chemical stimuli

Multiunit smooth muscle

This type is found in large arteries, the large airways in the lungs, erector pili muscles of hair follicles and eye muscles which control the size of the pupil and control the focus of the eye. The multiunit smooth muscle:

Contains muscle fibres which are structurally different to each other

Each fibre contains a vast number of nerves, which when bound to other fibres, forms a motor unit

Responds to neural stimulation

Both single-unit and multiunit smooth muscles are stimulated by the autonomic nervous system, hence is also responsive to hormonal control. (Human Anatomy and Physiology 8th Edition, Marieb and Koehn, Pearson)

Contraction and relaxation of smooth muscle

The action potential of smooth muscle dissipates through the fibres slowly and uncertainly. It is produced by L-type calcium channels, and it is through this route calcium influx occurs. The cells also posses ligand gated cation channels, which also controls calcium influx when activated. Calcium ions are released from the sarcoplasmic reticulum when the IP3 receptor is activated. IP3 is generated by the activation of many types of G-protein-coupled receptor. Therefore, calcium ions can be released through the stimulation of these receptors, without the membrane bcoming depolaried. (Human Anatomy and Physiology 8th Edition, Marieb and Koehn, Pearson, Pharmacology 6th edition, Rang et al)

Contraction is initiated when the myosin light chains are phosphorylated, causing it to be detached from actin filaments. This reaction is catalyed by myosin light chain kinase, which is activated when it interacts with calmodulin, which in turn is bound to calcium ions. (Pharmacology 6th Edition, Rang et al)

The ATP-efficient contraction of smooth muscle is vital to body homeostasis. The smooth muscle present in small arterioles and other visceral organs displays a moderate degree of contraction, known as smooth muscle tone, without fatiguing, and requires low amount of energy to facilitate this process. (Human Anatomy and Physiology 8th Edition, Marieb and Koehn, Pearson)

Relaxation involves a number of complexes processes, such as calcium detachment from calmodulin, active transport of calcium into the sarcoplasmic reticulum and extracellular fluid, and the activation of the enzyme myosin phosphatase which reverses the phosphorylation of myosin causing relaxation. The activity of both myosin phosphatase and myosin light chain kinase provides a balance, and are regulated by cyclic nucleotides - cAMP and cGMP. Below is a diagrammatic impression of the processes involved during contraction:

(Human Anatomy and Physiology 8th Edition, Marieb and Hoehn , Pearson, )

Regulation of contraction

Different autonomic nerves affiliated to smooth muscles of visceral organs release different neurotransmitters which exert different effects on a particular group of smooth muscle cells. The effect of a specific neurotransmitter on a particular smooth muscle cell depends on the type of receptor on the sarcolemma. An example is the binding of acetylcholine to acetylcholine receptors on smooth muscle in the bronchioles; the muscle contracts leading to the narrowing of the bronchioles. When noradrenaline, released by a different autonomic nerve fibre, binds to the same group of receptors it causes relaxation and hence bronchiole dilation. However, the binding of noradrenaline binds to smooth muscles in the walls of most blood vessels, it causes contraction and hence vessel constriction. (Human Anatomy and Physiology 8th Edition, Marieb and Koehn, Pearson)

Some smooth muscle have no nerve supply. As a result they depolarise spontaneously or in response to chemical molecules which bind to G-protein-coupled receptors. Chemical factors that cause contraction without membrane depolarisation include hormones, histamine, low pH, lack of oxygen and excess carbon dioxide. Some smooth muscle respond to both chemical and neural stimuli. (Human Anatomy and Physiology 8th Edition, Marieb and Koehn, Pearson)

Acetylcholine

The muscarinic and nicotinic effects of acetylcholine was demonstrated by Henry Dale’s experiment on cats. Small and medium doses (2mg and 50mg) of acetylcholine produces a fall in blood pressure in cats due to vasodilatation. Atropine (2mg) is then added followed by 50mg acetylcholine which produces no effect in blood pressure, leading to the conclusion that atropine abolishes the muscarinic effect. However, a larger dose of atropine of 50mg produces an increase in blood pressure a nicotinic effect due to vasoconstriction. (Pharmacology 6th Edition, Rang et al)

The pharmacological classification highlighted by Dale corresponds to the function of acetylcholine iin vitro. The muscarinic affects are produced by the release of acetylcholine at postganglionic parasympathetic nerve endings, with 2 exceptions:

Acetylcholine causes vasodilatation, although most blood vessels have no parasympathetic innervation. Acetylcholine acts on vascular endothelial cells to release nitric oxide to cause smooth muscle relaxation.

Acetylcholine causes secretion from sweat glands which are innervated by sympathetic nervous system.

The nicotinic actions are produced by the action of acetylcholine exerting its effects on:

autonomic ganglia of the sympathetic and parasympathetic systems

the motor end plate of voluntary muscle

secretory cells of adrenal medulla.

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