Smooth muscle and hormones

Question 1

How does actin and myosin affect muscle contraction- smooth muscle

Answer 1

1. Action potential arrives at the smooth muscle cells causing sodium channels to open and sodium influx, this will cause depolarisation.
2. Depolarisation open the voltage gated calcium ion channels causing calcium ion influx from the extracellular space
3. Calcium ions bind to calmodulin to form a calcium-calmodulin complex.
4. The calcium-calmodulin complex activates the myosin light chain kinase (MLCK).
5. MLCK phosphorylates the myosin heads.
6. The phosphorylated myosin heads form cross bridges with the actin filament.
7. The sliding filament power stroke occurs
8. Myosin light chain phosphatase (MLCP) dephosphorylate the myosin head, stopping the cross-bridge.
9. Ca+2 pumps return intracellular Ca+2 to normal.

Question 2

Difference in smooth muscle compared to skeletal muscle

Answer 2

Ca+2 influx, cross bridge formation (activity of MLCK) and Ca+2 removal takes longer in smooth muscle compared to skeletal muscle. Smooth muscle is more stretchable allowing organs to expand whilst retaining their ability to contract.

Question 3

Where is smooth muscle found

Answer 3

GI tract, airways, skin and blood vessels

Question 4

Structure of smooth muscle cell

Answer 4

Smooth muscle is spindle shaped, it is thickest in the middle whilst it tapers at each end, it also has a centrally located nucleus. It has dense bodies which anchor the thin filament. It contains thick and think filament for contraction of the muscle cell. The sarcoplasmic reticulum is located very close to the caveolae, which are indentations of the plasma membrane. The caveolae increases the surface area of the plasma membrane and has a high density of voltage gated calcium channels. Can be organised in single or multi-units

Question 5

Single unit smooth muscle cells

Answer 5

The cells work as one body, when one cell depolarises the others do as well. The cells are connected by gap junctions so ions flow freely between the smooth muscle cells

Question 6

Multi unit smooth muscle cells

Answer 6

The cells are separated from each other so when one cell depolarises it does not mean that the others will depolarise.

Question 7

Skeletal muscle structure

Answer 7

1) Composed of multiple muscle fascicles which are wrapped together in the epimysium.
2) Each fascicle is composed of bundles of muscle fibre that are wrapped in the perimysium.
3) The perimysium separates the fascicles from each other.
4) Each muscle fibre is an individual muscle cell wrapped in endomysium.
5) It contains myofibrils which are made of thick (myosin) and thin (actin) filaments.

Question 8

Structures within the myofibril

Answer 8

Sarcolemma- plasma membrane
Sarcomere- repeated contractile units between two Z-disks
Transverse (T) tubule- extension of the sarcolemma which penetrates deep into the muscle fibre, connected to sarcoplasmic reticulum
Sarcoplasmic reticulum- specialised ER which stores calcium ions
Triad- combination of sarcoplasmic reticulum and T-tubule which interact via the terminal cristernae

Question 9

Structure of sarcomere

Answer 9

M line- centre of sarcomere
I band- area which contains only thin (actin) filament
Z band- centre of thin actin filament, between two Z bands is a sarcomere
A band- Where there is thick (myosin) filament, the darker region is where there is overlap between the the thick and thin filament. The lighter region is where there is only the thick filament and is the H zone.

Question 10

Troponin-tropomyosin complex

Answer 10

Interacts with the actin filament. made of 3 types of Troponin. One is Troponin T which binds to tropomyosin, then Troponin C which binds calcium ions and finally Troponin 1 which binds actin. The myosin binding site is blocked by the troponin-tropomyosin complex.

Question 11

Contraction of skeletal muscles (excitation-contraction model)

Answer 11

1) When an action potential arrives at the terminal axon in the neuron it triggers calcium influx and fusion of the synaptic vesicles with the presynaptic membrane, at the neuromuscular junction.
2) The ACh will diffuse across the synaptic cleft and will bind to the N1 receptor. These are coupled with the sodium ion channels which will open allowing sodium influx and depolarising the sarcolemma and the T-tubule.
3) This depolarisation will cause the opening of the calcium ion channels in the sarcoplasmic reticulum, calcium enters the cytoplasm.
4) The Calcium binds with tropanin C, inducing a confirmation change in the troponin-tropomyosin complex.
5) The complex removes itself exposing the myosin binding site, allowing the actin to interact with myosin. Causing cross bridges to form and muscle contraction.

Question 12

Relaxation of skeletal muscle

Answer 12

The calcium ions will be pumped back into the sarcoplasmic reticulum. Terminating the contraction event. As there is no calcium available, the troponin-tropomyosin complex will block the myosin binding site on the actin, meaning no cross bridge can form.

Question 13

The sliding filament theory of muscle contraction

Answer 13

• The ATP on the myosin head is hydrolysed to ADP and inorganic phosphate. The myosin head undergoes a conformation change, getting it ready to attach to the actin.
• Myosin head attaches itself to the myosin binding site on the actin, forming a cross-bridge.
• The myosin filament pulls the actin filament towards the M-line, this is a power stroke and causes the myosin head to become smaller.
• The ADP and inorganic phosphate are released from the myosin head and a new ATP molecule is attached to the myosin head.
• This attachment with ATP detaches the myosin head from the actin, allowing more cross-bridges to be formed.
• The ATP hydrolyses causes a change in the conformation of the myosin head and the process is repeated.

Question 14

Hormone

Answer 14

A chemical messenger synthesised by a specific tissue and secreted into the blood stream where it is carried to a non-adjacent site in the body to exert its action. They are secreted by glands in the endocrine system and control and regulate processes like homeostasis and reproduction

Question 15

The endocrine system

Answer 15

Means internal secretion, tissues which release hormones are known as endocrine tissues

Question 16

Endocrine signalling

Answer 16

A cell signals to a distant cell via a chemical messenger released in the circulatory system

Question 17

Paracrine signalling

Answer 17

A cell communicates to a cell next to it, i.e. a neighbouring cell in the same tissue

Question 18

Autocrine signalling

Answer 18

A cell signals to itself i.e. the same cell that released the chemical is stimulated. Cytokines often use this type of signalling.

Question 19

Synaptic or Neurocrine signalling

Answer 19

A neuron signals to a cell using neurotransmitters. This signalling is really just a special type of paracrine signalling.

Question 20

Hormone control- negative feedback

Answer 20

When the hormone is no longer needed and homeostasis is achieved the pathway is shut off. As rising levels of the hormone are detected a signal will be sent to reduce its release. Prevents the system from becoming overactive as the mechanism is inhibited by its own products. It decreases the response and brings it back to the set (homeostatic) point. Example- insulin and ADH

Question 21

Hormone control- neuronal, substrate and tropic

Answer 21

Neuronal stimulation is when hormones are released due to the action of neurons i.e CRH. Tropic hormones are released in response from another hormone, i.e. ACTH. Substrate control is when the hormone is directly influenced by the circulating volumes of the substrate it is controlling, like glucose and insulin.

Question 22

Hormonal control- positive feedback

Answer 22

Amplifies a particular response so that it deviated further from the set (homeostatic) point. Requires an external factor to break the positive feedback loop. Example- oxytocin during childbirth

Question 23

Hypothalamic-pituitary axis

Answer 23

The Hypothalamus is located at the base of the forebrain. It can receive circulatory inputs (from the blood stream) and neuronal inputs (emotions). The inferior part of the hypothalamus gives rise to the pituitary stalk. The pituitary gland is split into two lobes, the anterior pituitary and the posterior pituitary. Provides a link between endocrine and neuronal system

Question 24

The two lobes of the pituitary gland

Answer 24

The posterior pituitary gland (Neurohypophysis) stores hormones made by the hypothalamus, and the anterior pituitary gland (adenohypophysis) synthesises hormones. In both lobes the hypothalamus controls the secretion of hormones by the pituitary, the mechanisms are very different.

Question 25

How the posterior pituitary gland is control

Answer 25

Neurohormones from the hypothalamus are secreted directly into the capillary plexus which is in the posterior pituitary so they can be stored

Question 26

How the anterior pituitary gland is controlled

Answer 26

stimulatory and inhibitory neurohormones from the hypothalamus are secreted into the extracellular fluid at the median eminence. They can then be picked up by the capillary plexus and transported down the portal vein into the secondary capillary plexus where they can be released into the anterior pituitary gland. Effecting whether it produces hormones. Each hormone is synthesised by a particular troph which is a collection of cells named after what they produce.

Question 27

Growth hormone (GH)

Answer 27

Synthesised by= Somatotrophs in the anterior pituitary gland
Stimulated by= GHRH
Inhibited by= GHIH & IGF-1
Target organ= Liver
Effect= stimulates growth

Question 28

Thyroid stimulating hormone (TSH)

Answer 28

Synthesised by= Thyrotrophs in the anterior pituitary gland
Stimulated by= TRH
Inhibited by= T3
Target organ=Thyroid organ
Effect= stimulates throid hormone release

Question 29

Follicle stimulating hormone (FSH) and Luteinizing hormone (LH)

Answer 29

Synthesised by= Gonadotrophs in the anterior pituitary gland
Stimulated by= GnRH & sex steroids
Inhibited by= prolactin and sex steroids
Target organ= reproductive organs
Effect= Stimulates sex steroid production

Question 30

Prolactin

Answer 30

Synthesised by= Lactotrophs in the anterior pituitary gland
Stimulated by= PRF & TRH
Inhibited by= Dopamine
Target organ= Mammary glands and reproductive organs
Effect= Stimulates milk production

Question 31

Adrenocorticotropic hormone (ACTH)

Answer 31

Synthesised by= Corticotropes in the anterior pituitary gland
Stimulated by= CRH
Inhibited by= Glucocorticoids
Target organ= Adrenal cortex
Effect= stimulates cortisol release

Question 32

Hormones produced by the posterior pituitary gland

Answer 32

Oxytocin- causes contraction on smooth muscle in the uterus leading to birth and in the mammary gland leading to milk ejection.
Antidiuretic hormone (ADH)- increases permeability of collecting duct

Question 33

Diseases caused by dysregulation of hormone production in the HP axis.

Answer 33

Acromegaly: Excess growth hormone production by pituitary gland after the growth plates are formed, leaving to enlarged organs and physical deformities
Cranial diabetes insipidus: ADH deficiency due to lack of hypothalamic synthesis, leads to increases thirst and dilute urine

Question 34

Synthesis of steroid hormones

Answer 34

CHOLESTEROL is converted to PREGNENOLONE by the enzyme desmolase, it removes 6 carbons from ring D in the mitochondria. Pregnenolone is then converted to progesterone by enzymes in the mitochondria and cytoplasm. This involves isomerisation, the double bond moves from ring B to ring A. The hydroxyl group on ring A becomes a keto group. Steps after this are variable but progesterone tends to be converted into androgens (testosterone) or mineralocorticoids (aldosterone)

Question 35

Steroid hormone release

Answer 35

Released immediately by diffusing out of the cell. Rate of release depends on rate of synthesis. They are lipid soluble so travel in the blood attached to plasma proteins

Question 36

How steroid hormones act on receptors

Answer 36

The hormones diffuse across the plasma membrane and bind to intracellular receptors on the hormone binding site, they can be on any organelle in the cytoplasm. This will cause a shape change due to the flexible hinge region. The inhibitory protein will move away from the receptor exposing the DNA binding site. The activated hormone will travel to the nucleus (if it isn’t already there) and bind to the hormone response element of DNA which will affect transcription of specific genes. Increasing or decreasing the synthesis of mRNA. The mRNA will then be translated to a protein altering cell activity.

Question 37

Cell surface receptors

Answer 37

Used for polypeptide and modified amino acids hormones as they cannot cross the cell membrane, The hormone binds to the extracellular domain causing a conformational change in the intracellular domain allowing it to pass on the message via transduction via relay proteins and second messengers. This activates our cellular processes.

Question 38

G-protein coupled receptor

Answer 38

G protein has three subunits; alpha, beta and gamma. In the resting state the alpha sub-unit has GDP bound to it, with the beta and gamma bound to the alpha subunit. When the hormone binds to the extracellular surface of the receptor, the G protein complex changes shape, losing GDP and gaining GTP, this cause the alpha subunit to split away from the beta and gamma subunit. The alpha subunit is activated which will phosphorylate and activate an effector protein using the phosphate from GTP as its hydrolysed to GDP. The effector protein will activate a second messenger such as cAMP, which could trigger an enzyme cascade bringing about a change in cellular response.

Question 39

Tyrosine kinase receptor

Answer 39

The Tyrosine kinase receptor contains the alpha and beta subunit which are two monomers. When a hormone binds to a receptor it causes a change in shape, which will causer dimerization, so the two monomers will become physically closer together. This will activate the kinase and cause phosphorylation of our intracellular tyrosine residues using energy from ATP. As the ATP breaks down into ADP and phosphate which will phosphorylate the tyrosine. The phosphorylated tyrosine residues can now bind to specific relay proteins which can trigger an enzyme cascade and cause different cellular responses often via signal transduction pathways. Used by insulin

Question 40

Intracellular receptors

Answer 40

are used for steroids and hydrophobic hormones. In its resting state the intracellular receptor is in the cytoplasm. When the hormone crosses the plasma membrane it binds to the intracellular receptor causing a conformational change, activating the receptor. The hormone and receptor together will enter the nucleus (unless they are already there) and bind to specific sections of the DNA called hormone response elements. This will cause a change in protein synthesis by either inhibiting or stimulating the transcription of certain genes.

Question 41

Adenylate cyclase

Answer 41

An effector protein which converts ATP to cAMP, which is a second messenger. It can trigger protein kinase and trigger a range of cellular responses such as opening an ion channel. This is used by glucagon, FSH, ACTH and others.

Question 42

Phospholipase C

Answer 42

Acts as an effector protein. Acts on PIP2 which is in the membrane. PIP2 breaks down into IP3 and DAG. IP3 binds to the endoplasmic reticulum, opening a ligand gated ion channel releasing calcium into the cytoplasm which can activate multiple cellular responses. IP3 is the second messenger. Used by catecholamines, ADH, oxytocin and others.

Question 43

Steroid hormones

Answer 43

Synthesised from cholesterol. . Because they are soluble in fat they can pass through the plasma membrane and bind to intracellular receptors. Because they are hydrophobic they can not travel freely in the bloodstream but bind to plasma proteins. They act on the nucleus meaning they have a slow mechanism of action. Example= cortisol

Question 44

Non-steroid hormones

Answer 44

Divided into polypeptide hormones and modified amino acid hormones. Polypeptide hormones are the majority of hormones ie insulin. Modified amino acid hormones are made from tyrosine and trytophan precursors ie adrenaline. Non-steroid hormones are water soluble but not fat soluble meaning they have to bind to receptors on the cell surface membrane and cant pass straight through. So they exert their effects on the membrane not the nucleus, so are fast acting

Question 45

Polypeptide hormone synthesis, storage and release

Answer 45

Synthesised through transcription and translation. Stored in secretory vesicles as the hormone is water soluble and can not just diffuse out of the cell. The vesicles are released by exocytosis, they fuse with the plasma membrane then release their contents outside the cell.

Question 46

Amino acid hormone synthesis, storage and release

Answer 46

Synthesised from a precursor, either Tyrosine or Tryptophan. Stored in secretory vesicles and released by exocytosis, diffuse in the blood. The thyroid hormone works differently.

Question 47

Adrenal gland

Answer 47

Controlled by the Hypothalamus-pituitary-adrenal-axis. Part of the sympathetic nervous system. It is located above the kidneys and is divided into two layers- adrenal medulla and adrenal cortex, there is a capsule around the outside of the two layers.

Question 48

Hypothalamus-pituitary-adrenal-axis

Answer 48

The Hypothalamus detects the stress and releases CRH. This acts on the anterior pituitary gland causing the release of ACTH. This acts on the endocrine tissue of the adrenal gland which will release cortisol. Direct stimulation from the sympathetic nervous system causes adrenaline to be release.

Question 49

Adrenal medulla

Answer 49

• Controlled by sympathetic nervous system
• Made of types of neuro-endocrine cells. The neuro-adrenaline secreting cells and the adrenaline secreting cells.
• Secretes catecholamines (modified amino acid hormones). They are stored in neuro-endocrine granules and are released in response to a fight or flight response. Increases heart rate

Question 50

Adrenal cortex

Answer 50

Primarily regulated by ACTH. Divided into the zona glomerulosa, zona fasciculata, and zona reticularis. All secrete steroid hormones

Question 51

Zona glomerulosa

Answer 51

Secretes mineralocorticoids (aldosterone) to regulates sodium reabsorption and blood volume, very small. Outside layer next to capsule

Question 52

Zona faciculata

Answer 52

Composed of rod like cells which secretes glucocorticoids (mainly cortisol) - involved stress response, increasing blood glucose levels. Bigger. Middle layer

Question 53

Zona reticularis

Answer 53

Secretes the androgen precursor, DHEA (dehydroepiandosterone) & glucocorticoids. Innermost layer nest to the medullary vein

Question 54

Dysregulation of the adrenaline gland

Answer 54

• Endocrine function of the adrenal gland must be tightly regulated
• Excess aldosterone - water retention leading to hypertension. Can be caused by tumour (Conn’s syndrome) or excess medication and other disorders
• Excess cortisol - Cushing’s syndrome. Can lead to fat deposits and personality changes. Can be caused by tumour (Cushing’s disease) or excess medication
• Adrenal cortex insufficiency (less cortisol and aldosterone) - Addison’s disease (destruction of cortex) or caused by secondary disorders of hypothalamus and pituitary gland.