Browsing Pathways

Neurons are electrically excitable cells that process and transmit information through electrical and chemical signals. A neuron consists of a cell body, branched dendrites to receive sensory information, and a long singular axon to transmit motor information. Signals travel from the axon of one neuron to the dendrite of another via a synapse. Neurons maintain a voltage gradient across their membrane using metabolically driven ion pumps and ion channels for charge-carrying ions, including sodium (Na+), potassium (K+), chloride (Cl−), and calcium (Ca2+). The resting membrane potential (charge) of a neuron is about -70 mV because there is an accumulation of more sodium ions outside the neuron compared to the number of potassium ions inside. If the membrane potential changes by a large enough amount, an electrochemical pulse called an action potential is generated. Stimuli such as pressure, stretch, and chemical transmitters can activate a neuron by causing specific ion-channels to open, changing the membrane potential. During this period, called depolarization, the sodium channels open to allow sodium to rush into the cell which results in the membrane potential to increase. Once the interior of the neuron becomes more positively charged, the sodium channels close and the potassium channels open to allow potassium to move out of the cell to try and restore the resting membrane potential (this stage is called repolarization). There is a period of hyperpolarization after this step because the potassium channels are slow to close, thus allowing more potassium outside the cell than necessary. The resting potential is restored after the sodium-potassium pump works to exchange three sodium ions out per two potassium ions in across the plasma membrane. The action potential travels along the axon and upon reaching the end, causes neurotransmitters such as serotonin, dopamine, or norepinephrine to be released into the synapse. These neurotransmitters diffuse across the synapse and bind to receptors on the target cell, thus propagating the signal.

Kidneys are regulatory organs involved in removing wastes from the blood, hormone production, nutrient reabsorption, and regulating electrolyte concentrations, acid-base balance, extracellular fluid volume, and blood pressure. The early proximal tubule is where glucose, amino acids, sodium, chlorine, phosphate, bicarbonate, and water are reabsorbed. Only water is reabsorbed in the thin descending loop of Henle, while sodium, chlorine and potassium are reabsorbed in the thick ascending loop of Henle. Sodium and chlorine are also reabsorbed in the early distal convoluted tubule. Finally, sodium and water are reabsorbed in the collecting tubules. Blood pressure is regulated by the hormones angiotensin II and aldosterone, which increases sodium chloride reabsorption. This results in an expansion of the extracellular fluid compartment, thus increasing blood pressure.

Angiotensin is a peptide hormone that is part of the renin-angiotensin system responsible for regulating fluid homeostasis and blood pressure. It is involved in various means to increase the body's blood pressure, hence why it is a target for many pharmceutical drugs that treat hypertension and cardiac conditions. Angiotensin II, the primary agent to inducing an increased blood pressure, is formed in the general circulation when it is cleaved from a string of precursor molecules. Angiotensinogen is converted into angiotensin I with the action of renin, an enzyme secreted from the kidneys. From there, angiotensin I is converted to the central agent, angiotensin II, with the aid of angiotensin-converting enzyme (ACE) so that it is available in the circulation to act on numerous areas in the body when an increase in blood pressure is needed. Angiotensin II can act directly on receptors on the smooth muscle cells of the tunica media layer in the blood vessel to induce vasoconstriction and a subsequent increase in blood pressure. However, it can also influence the blood pressure by aiding in an increase of the circulating blood volume. Angiotensin II can cause vasopressin to be released, which is a hormone involved in regulating water reabsorption. Vasopressin is created in the supraoptic nuclei and they travel down the neurosecretory neuron axon to be stored in the neuronal terminals within the posterior pituitary. Angiotensin II in the cerebral circulation triggers the release of vasopressin from the posterior pituitary gland. From there, vasopressin enters into the systemic blood circulation where it eventually binds to receptors on epithelial cells in the collecting ducts of the nephron. The binding of vasopressin causes vesicles of epithelial cells to fuse with the plasma membrane. These vesicles contain aquaporin II, which are proteins that act as water channels once they have bound to the plasma membrane. As a result, the permeability of the collecting duct changes to allow for water reabsorption back into the blood circulation. Angiotensin II also has an effect on the hypothalmus, where it helps trigger a thirst sensation. Correspondingly, there will be an increase in oral water uptake into the body, which would then also increase the circulating blood volume. Another way that angiotensin II helps increase the blood volume is by acting on the adrenal cortex to stimulate aldosterone release, which is responsible for increasing sodium reuptake in the distal convoluted tubules and the collecting duct. It is formed when angiotensin II binds to receptors on the zona glomerulosa cells in the adrenal cortex, which triggers a signaling cascade that eventually activates the steroidogenic acute regulatory (StAR) protein to allow for cholesterol uptake into the mitochondria. Cholesterol then undergoes a series of reactions during steroidogenesis, which is a process that ultimately leads to the synthesis of aldosterone from cholesterol. Aldosterone then goes to act on the distal convoluted tubule and the collecting duct to make them more permeable to sodium to allow for its reuptake. Water subsequently follows sodium back into the system, which would therefore increase the circulating blood volume. In addition, potassium and hydrogen are also being excreted into the urine simultaneously to maintain the electrolyte balance.

Tubular striated muscle cells (i.e. skeletal and cardiac myocytes) are composed of bundles of rod-like myofibrils. Each individual myofibril consists of many repeating units called sarcomeres. These functional units, in turn, are composed of many alternating actin and mysoin protein filaments that produce muscle contraction. The muscle contraction process is initiated when the muscle cell is depolarized enough for an action potential to occur. When acetylcholine is released from the motor neuron axon terminals that are adjacent to the muscle cells, it binds to receptors on the sarcolemma (muscle cell membrane), causing nicotinic acetylcholine receptors to be activated and the sodium/potassium channels to be opened. The fast influx of sodium and slow efflux of potassium through the channel causes depolarization. The resulting action potential that is generated travels along the sarcolemma and down the T-tubule, activating the L-type voltage-dependent calcium channels on the sarcolemma and ryanodine receptors on the sarcoplasmic reticulum. When these are activated, it triggers the release of calcium ions from the sarcoplasmic reticulum into the cytosol. From there, the calcium ions bind to the protein troponin which displaces the tropomysoin filaments from the binding sites on the actin filaments. This allows for myosin filaments to be able to bind to the actin. According to the Sliding Filament Theory, the myosin heads that have an ADP and phosphate attached binds to the actin, forming a cross-bridge. Once attached, the myosin performs a powerstroke which slides the actin filaments together. The ATP and phosphate are dislodged during this process. However, ATP now binds to the myosin head, which causes the myosin to detach from the actin. The cycle repeats once the attached ATP dissociates into ADP and phosphate, and the myosin performs another powerstroke, bringing the actin filaments even closer together. Numerous actin filaments being pulled together simultaneously across many muscles cells triggers muscle contraction.

Gastric acid plays a key role in the digestion of proteins by activating digestive enzymes to break down long chains of amino acids. In addition, it aids in the absorption of certain vitamins and minerals and also acts as one of the body's first line of defence by killing ingested micro-organisms. This digestive fluid is formed in the stomach (specifically by the parietal cells) and is mainly composed of hydrochloric acid (HCl). However, it is also constituted of potassium chloride (KCl) and sodium chloride (NaCl). The main stimulants of acid secretion are histamine, gastrin, and acetylcholine which all, after binding to their respective receptors on the parietal cell membrane, trigger a G-protein signalling cascade that causes the activation of the H+/K+ ATPase proton pump. As a result, hydrogen ions are able to be pumped out of the parietal cell and into the lumen of the stomach. The hydrogen ions are available inside the parietal cell after water and carbon dioxide combine to form carbonic acid(the reaction is catalyzed by the carbonic anhydrase enzyme) which dissociates into a bicarbonate ion and a hydrogen ion. Moreover, the chloride and potassium ions are transported into the stomach lumen through their own channels so that hydrogen ions and/or potassium ions can form an ionic bond with chloride ions to form HCl and/or KCl, which are both constituents of stomach acid. In addition, the peptide hormone somatostatin is the main inhibitor to gastric acid secretion. Not only does it inhibit the G-protein signalling cascade that leads to proton pump activation, but it also directly acts on the enterochromaffin-like cells and G cells to inhibit histamine and gastrin release, respectively.

The pancreas is crucial in many organisms for properly converting food into usable fuel to be used by cells. It acts as part of the digestive system for a majority of its function as it is connected to the stomach and provides digestive enzymes to the partly digested food brought in by the stomach. The pancreas also serves as an endocrine component, by creating hormones to regulate blood sugar. Insulin, a hormone created by the pancreas (beta cells), acts to lower blood sugar, which is very important as it allows cells in the body to use sugar without inducing hyperglycaemia.

Angiotensin is a peptide hormone that causes vasoconstriction and a subsequent increase in blood pressure. It is part of the renin-angiotensin system, which is a major target for drugs that lower blood pressure. Angiotensin also stimulates the release of aldosterone, another hormone, from the adrenal cortex. Aldosterone promotes sodium retention in the distal nephron, in the kidney, which also drives blood pressure up.

Gastric acid is a digestive fluid, formed in the stomach. Gastric acid is produced by cells lining the stomach, which are coupled to systems to increase acid production when needed.

Kidneys are regulatory organs involved in removing wastes from the blood, hormone production, nutrient reabsorption, and regulating electrolyte concentrations, acid-base balance, extracellular fluid volume, and blood pressure. The early proximal tubule is where glucose, amino acids, sodium, chlorine, phosphate, bicarbonate, and water are reabsorbed. Only water is reabsorbed in the thin descending loop of Henle, while sodium, chlorine and potassium are reabsorbed in the thick ascending loop of Henle. Sodium and chlorine are also reabsorbed in the early distal convoluted tubule. Finally, sodium and water are reabsorbed in the collecting tubules. Blood pressure is regulated by the hormones angiotensin II and aldosterone, which increases sodium chloride reabsorption. This results in an expansion of the extracellular fluid compartment, thus increasing blood pressure.

Muscle contractions occur when the myocyte is depolarized enough for an action potential to occur. Depolarization is caused by acetylcholine released from the adjacent motor neuron, which activates nicotinic acetylcholine receptors and opens the sodium/potassium channel. The fast influx of sodium and slow efflux of potassion trigger the action potential. This action potential activates L-type voltage-dependent calcium channels on the membrane and ryanodine receptors on the sarcoplasmic reticulum, both which cause calcium ions to be released into the cytosol. In smooth muscle, ionic calcium induces muscle contraction by binding to and activating myosin light chain kinase, while in striated muscle contraction results from ionic calcium binding to and activating troponin C.