Gibbs-Donnan Effect on Resting Membrane Potential

Gibbs-Donnan Effect on Resting Membrane Potential How the Gibbs-Donnan equilibrium conditions and diffusion through a semipermeable membrane are involved in creating the resting membrane potential Introduction The resting membrane potential (RMP) is an electrical potential difference in cells, occurring across their plasma membranes. The cytoplasm of the cell is electrically negative in comparison to the surrounding extracellular fluid, this difference in electrical charge gives rise to the RMP. The RMP is essential for the functioning of many electrically excitable cells including, neuronal cells, smooth and skeletal muscle cells, as well as cardiac myocytes, which through electrical impulses control the contractility of the heart. During this essay the generation of the resting membrane potential will be explored, including the effects of the Gibbs-Donnan equilibrium conditions, the structure and function of the plasma membrane, and how, with the diffusion of ions through a semi permeable membrane they give rise to the RMP. (Levy, N. et al.2006) Plasma Membrane The plasma membrane asserts tight control over the interstitial environment of the cell, this is achieved through the formation of a phospholipid bilayer containing protein constituents (ref). Phospholipids are distributed into two leaflets within the bilayer, with the hydrophobic portions facing inwards and the hydrophilic tails of the phospholipids facing the aqueous environment, the presence of phospholipids give the membrane its capacitance. Integral membrane proteins and ion channel proteins span the length of the membrane, like that of the Na+-K+ pump and Sodium-Potassium leak channels discussed later, which aid in the conductance of the cell membrane. The inter and extracellular surfaces of the membrane are negatively charged, due to the presence of acidic phospholipids and the anionic nature of proteins at biological pH, this negative charge on the outer membranes with respect to extra and intracellular fluid is known as the zeta potential, which causes the formation of a sma ll electrical field (ref); This electrical field works to achieve electroneutrality with opposing charged particles, and by doing so aids in the formation of concentration gradients. Changes to surface charges within the plasma membrane, such as ionic concentrations, can therefore effect the resting membrane potential and the ability of a cell to reach threshold (Sperelakis, N. 1998). Concentration gradient and Electrical Potential To understand how the flow of ions contribute to the RMP, the formation of a concentration gradient and electrical potential must first be understood. Molecules diffuse from an area of high concentration to an area of lower concentration, if two aqueous compartments separated by a membrane were formed, containing equal concentrations of the X molecule then no diffusion would occur between compartments (Figure 1). However if the concentration of X increased in compartment A, then the ion would flow down its concentration gradient into compartment B until equilibrium is reached between compartments. However diffusion is more complexed in biological compartments as ions are found in the form of cations and anions. If an X+ion was placed in compartment A, which contained a higher concentration of X+than compartment B, then X+ would again flow down its concentration gradient into compartment B, however X+ now also flows against its concentration gradient back into compartment A, due to th e electrical potential difference across the membrane, generated by the loss of cations from compartment A, causing an increase in negativity, and an increase in X+in compartment B, increasing electrical charge opposing cations (Figure 2); This movement of ions causes a potential difference to arise between compartments, increased movement of X+ down its concentration gradient, increases the potential difference, and decreases the ability of X+ to move against its electrical gradients, thus an equilibrium is reached between the concentration gradient and electrical gradient, known as the equilibrium potential (Aidley, D.1989). Gibbs-Donnan Equilibrium The cytoplasm of eukaryotic cells contain permeable ions as well as many impermeable ionised molecules that cannot penetrate the cell membrane, such as proteins, nucleic acids and glycoproteins. Many of these intracellular molecules are negatively charged at physiological pH, causing a notable effect on the concentration gradient and electrical potential of permeable cations and anions across the plasma membrane. The effect of impermeable intracellular anionic molecules therefore influences the resting membrane potential, this is known as a Gibbs-Donnan equilibrium. Again consider two aqueous compartments separated by a semi permeable membrane, compartment A contains Na+ and proteins (Pr-), compartment B contains Na+ and Cl- (Figure 3a). The semi permeable membrane is permeable to Na+, Cl- and Water but impermeable to Pr-. Compartment A and B contain 0.1 molar solutions of Na protinate and NaCl respectively, as the concentration of Cl- is higher in compartment B it diffuses down its concentration gradient into compartment A, this is turn causes the creation of an electrical potential as compartment A increases in negativity due to the anionic properties of Cl-, prompting a flux of K+ down its electrical gradient from compartment B to A. Equilibrium will eventually occur between compartments so that the concentration of Na+ and Cl- are equal (Figure 3b): [Na+]A[Cl-]A= [Na+]B[Cl-]B This is known as Gibbs-Donnan equilibrium conditions (Sperelakis, N.1998). However it must be noted from the equations that only the permeate ions satisfy the gibbs-donnan equilibrium conditions, the impermeable Pr- are not included as they are unable to diffuse and reach equilibrium (Sperelakis, N.1998). Applying the Nernst equation for either Na+ or Cl- results in a negative electrical potential, this is due to the impermeable protein ions in chamber A (Sperelakis, N.1998), these negative impermeable intracellular anions therefore contribute to the negativity of the cytoplasm in relation to the extracellular fluid, contributing to the resting membrane potential (Donnan, F). Another property of Gibbs-Donnan equilibria should be noted, looking at figure 3b it can be seen that the net concentration of NaCl in chamber A is greater than that of chamber B, this is due to the presence of protein anions in chamber A when establishing electrochemical equilibrium between ions, and is a general property of Gibbs-Donnan equilibria (Levy, N. et al.2006). Finally it is important to mention the equilibrium state of water, as previously mentioned chamber A contains a higher concentration of ions than chamber B, therefore there is a large osmotic gradient between the two chambers; This leads to a flux of water from chamber B to A, however, the osmotic effects of water influx on chamber A acts to dilute ion concentrations building up within the chamber, therefore hydrostatic pressure in chamber A would be insufficient to oppose water influx, leading to a depletion of water and NaCl ions from chamber B (Sperelakis, N.1998); However this situation does not resemble true Gi bbs-Donnan equilibrium conditions, where by the build up of osmotic pressure in chamber A would resist the further osmotic influx of water, resulting in swelling of the chamber, if it were to be enclosed, such as a living cell (Sperelakis, N.1998). If unopposed gibbs-donnan equilibrium would cause the cytoplasm of living cells to have an osmotic pressure greater than that of the surrounding extracellular fluid, as water enters cells, control over cell volume may be lost (Sperelakis, N.1998). However this is not the case due to the cells ability to transport ions (Levy, N. et al.2006). Ion transport The resting membrane potential within skeletal muscle cells is around -80mV, this is due to the differing ion concentrations between the cytoplasm and surrounding extracellular fluid (ref), this difference in ion concentrations is maintained by the active transport of ions against there electrochemical gradient, powered by metabolic energy (ref). The ion pump of most importance to preserving potential difference across the cell membrane is the Na+/K+ATPase, this pumps out three Na+ in exchange for two extracellular K+, through the hydrolysis of a membrane bound ATPase, this ratio of 3:2 leaves the cytoplasm negative in respect to the extracellular fluid, and is therefore termed an electrogenic pump (Huang, F.et al.2009). Although the Na+/K+ATPase is responsible for only a small amount of the RMP between 12-16mV in skeletal myoblasts (Sperelakis, N.1998), overtime inhibition can lead to lack of cell excitability due to the accumulation of small depolarisations. Ion Diffusion To understand how Na+, K+ diffuse across the plasma membrane causing the RMP, their intra and extracellular concentrations must be established (Figure 4). Each ion is capable of establishing a RMP, therefore the potential depends on several factors, the permeability of the membrane to each ion, the intra and extracellular concentrations of each ion and the polarity of the ions (Guyton and Hall.2000). Firstly if the membrane is only permeable to a certain ion then that ion will be solely responsible for the generation of the RMP, for example, in a nerve fibre K+ concentration is greater in the cytoplasm than the extracellular fluid, if the membrane were only permeable to K+, then K+ would diffuse down its concentration gradient into the extracellular fluid until opposed by its electrical gradient, this would leave the cytoplasm with a negative charge of around -94mV with respect to the extracellular fluid, thus K+ would be responsible for a resting membrane potential of -94mV, as this is the Nernst potential for K+ (Guyton and Hall.2000). However the RMP cannot be caused by one ion alone, as the nerve cells has a RMP of -90mV, and the Nernsts potentials for K+ and Na+ are -94mV and +61mV respectively, therefore if the RMP was caused by one univalent ion it would be equal to that of their Nernst potential (Guyton and Hall.2000). Due to the Nernst potential of K+, it can be assumed that this ion is the major contributor to the RMP, the cytoplasmic concentration of K+ is 35times higher than that of its extracellular concentration, and it diffuses through the membrane via Potassium-Sodium leak channels in which its is 100 times more permeable to than Na+ (Guyton and Hall. 2000). However Na+ also contributes to the RMP by low amounts of Na+ diffusing through the Potassium-Sodium leak channels, this small amount of diffusion leads to a ratio of 0:1 Na+ in the cytoplasm to the extracellular fluid, giving a Nernst potential of +61mV (Guyton and Hall. 2000). Using the Nernst potentials for Na+ and k+ in theGoldman-Hodgkin-Katz equationtheir contribution to the RMP can be established, this results in an internal membrane potential of -86mV (Guyton and Hall. 2000). The remaining -4mV comes from the contribution of the previously mentioned electrogenic Na+-K+ pump, leading to a RMP of -90mV in nerve fibres (Guyton and Hall. 2000). Conclusion To conclude, the RMP arises due to a combination of several factors most of which have been covered in the preceding discussions. The cell membranes structural properties allow for the capacitance and conductance of electrical charges, as well as the generation of electrical fields due to the negatively charged outer membrane, this works to aid in the formation of concentration gradients by which ions flow. In the presence of ionic species which are unable to permeate the cell membrane, such as anionic intracellular proteins, a Gibbs-Donnan equilibrium occurs, in which the distribution of permeable ions favour the intracellular environment due to the presence of impermeable anionic molecules, this disruption of ionic concentrations across the plasma membrane coupled with the presence of impermeable anionic molecules, brings about a negative intracellular environment, and thus a potential difference across the membrane. However in a closed system such as the eukaryotic cell, the Gibbs -Donnan equilibrium leads to a greater intracellular osmotic pressure, if unopposed this would lead to a loss of control over cell volume, therefore ion transporters are in place to dissipate ion concentration, like that of the Na+-K+ ATPase. The exchange ratio of 3:2 potassium for sodium respectively, performed by the Na+-K+ ATPase also contributes to the electronegative intracellular environment, and thus the resting membrane potential. The major cause of the RMP is however down to the diffusion of potassium into the extracellular fluid via Sodium-Potassium leak channels, coupled with the low extracellular diffusion of sodium and the aforementioned Na+-K+ ATPase and Gibbs-Donnan equilibrium conditions, the resting membrane potential is formed. References Sperelakis, N. 1998. Cell Physiology Source Book. Second edition. Californa: Academic Press. Aidley, D. 1989. The Physiology of Excitable Cells. Third Edition. Cambridge: Cambridge University Press. Levy, N. et al. 2006. Principles of Physiology. Fourth edition. Philadelphia: Elsevier Mosby. Huang, F. el al. 2009. Distribution of the Na/K pumps turnover rates As a function of membrane potential, temperature, and ion concentration gradients and effect of fluctuations.Journal of Physical Chemistry B113(23), pp. 8096-8102.

Essay --

John Berger notes that, ‘original paintings are silent and still in a sense that information never is’. This observation is not different in the case of Vincent Van Gogh's Cafe Terrace at Night (1888). While visiting a museum, I stumbled across this painting, one of Vincent Van Gogh’s great works. My next move was to engage with the painting, with the aim of understanding critical information in relation to its meaning, significance and importance in both the traditional and modern context (Whitney et al, 360). This is to ensure that we learn more about the eye-catching paintings hanging on the walls of museums. In addition, this approach is vital in understanding both the literal and hidden meaning of such a painting, as intended by the artist. The name of the picture speaks volumes in relation to its context and setting; it is a night scene. From a literal perspective, the picture shows a large establishment where people from the region can enjoy their coffee by night. On the other hand, the picture also focuses on the expression of an important meaning in accordance with the intention and the aim of the painter in its composition. For instance, Van Gogh focuses on expressing a beautiful event aided by the stars and the bright sky. In addition, the painting integrates bright colors to express a peaceful encounter during a bright night (Brower 200). Firstly, I thought it would be satisfying to understand specific data in relation to the development of this painting. I asked myself; â€Å"When was this picture made?† Vincent Van Gogh’s the Cafà © Terrace, at Night 1888, was painted between the 9th and the 16th of September 1888. The next key question was the location. I learnt that the picture was painted in Arles. According to an obse... ...to different generations in the history of Arles (Punt et al, 228). In the 21st century, the painting still has a great meaning to the people of Arles. This indicates that the painting expresses a cultural relevance to the people of Arles in a similar manner to that which they felt in the 19th century. This attachment is valuable in enhancing my interaction with the painting. Analysis indicates that the painting has diverse meanings in relation to the type of interaction an individual has with the picture. The picture is never silent once you ask relevant questions such as its meaning, intention, and significance to the artist and the target audience. Moreover, the picture could be of meaning and relevance to individuals from different generations or centuries. This is because the painting has captured and exhibited a beautiful scene (The Drawings of Van Gogh 12).

British expansion into Africa between 1868 and 1902 Essay

To what extent were humanitarian and missionary motives the most important reason for British expansion into Africa between 1868 and 1902? Although there had been British presence in Africa from the start of the 19th Century, with British areas of control including Cape Colony, Orange Free State and areas along the West coast, prior to 1880 Britain had in reality very few possessions in Africa. Only when the ‘Scramble for Africa’ was triggered did Britain, along with many other European great powers, begin its campaign for territorial acquisition. The fundamental motives for British expansion into Africa were essentially the economic interest Africa held for Britain and its entrepreneurs, the rivalry Africa created between the Great European Powers, its strategic value and what was commonly presented to the British public as being the most important motive, humanitarian purposes. For many, including Colonial Secretary Joseph Chamberlain, it was believed that Britain had a moral obligation to bring civilization and Christianity to the native population who were considered to be ‘uncivilized’ and racially inferior. Moreover, the Church strongly promoted the idea of missionary work in Africa; the Church encouraged the notion that a fundamental element of imperial occupation was the extension of Christianity which therefore was a motive behind imperialism in Africa. Many missionary societies were created such as the United Society for the Propagation of the Gospel which conducted fund-raising activities and lectures. An example of a well known missionary was Mary Slessor who went to carry out her mission in Africa. Particularly concerned with tribal customs viewed as ‘un-Christian’, she set out to end human sacrifice, slavery and other forms of brutality. However, in reality humanitarian motives were of very limited significance in motivating British expansion into Africa; Britain was not simply guided by altruism and a quest to help the native populations, but instead was largely led by the economic and strategic interests the continent represented for it. Ultimately, it is likely that missionary incentives were simply conveyed as significant in order to win over public opinion and support, particularly through the media and popular entertainment. Of considerably greater significance to Britain was the strategic value that Africa held. Africa had always been strategically vital for Britain’s trade route to the Jewel of its Empire, India. Although Britain had few possessions in Africa before 1880, the few it did have included Gambia, Sierra Leone, Gold Coast and Cape Colony, all of which were deliberately very strategically situated along the coast. This provided Britain with stopping points and allowed it to ensure the security of its position along the long trade route to India. After the construction of the Suez Canal in 1969 Africa, and in particular Egypt, became of even greater strategic importance as the canal provided a quick route to India. As a result the canal attracted considerable British investment in Egypt and in the canal itself. This was illustrated when Britain invaded Egypt in 1882 in response to nationalist riots. British intervention demonstrated how Britain recognized the need to protect the financial investments in Egypt, and most importantly secure the route to India, despite Gladstone’s own personal policy of non-intervention. Moreover, it demonstrates how strategic considerations were ultimately only significant in order to protect Britain’s trade routes and its economic interests in Africa. However, the British occupation of Egypt in 1882 resulted in a turning point in European attitudes towards Africa. It was after this occupation that the ‘Scramble for Africa’ by European powers began, thus creating the issue of extreme rivalry between the Great powers, something which was very important in motivating formal British control in Africa. Until the 1880’s Britain felt no real need to establish formal territorial control, instead it relied on an ‘informal empire’ in which they had established a purely economic influence. Britain had not wished for territorial control in Africa which they recognized absorbed time, people and money but rather economic exploitation at minimum cost. Yet British seizure of Egypt meant that other European nations began to show expansionist interest in the region which in turn threatened Britain’s informal arrangement, particularly in West and Southern Africa. For example, Britain had an interest in Nigeria but a danger was that important trade along the River Niger would be under threat from French expansion in the area. Similar pressure came when Germany seized Togoland and the Cameroons in 1884 and the Belgians set up the Congo Free State in 1885. As a result the government granted a Royal Charter to the Niger Company, out of which eventually emerged the colony of Nigeria. It is unlikely that the government would have regarded the interests of the Niger traders very sympathetically had it not been for its determination not to allow France, Belgium and Germany from grabbing land which would threaten British trade, something which was of foremost importance to Britain and it would not allow to be compromised. The scramble in West Africa had also resulted in Berlin West Africa Conference which laid down rules for future annexation of territory. The treaty stated that in order to gain land a nation had to prove that they were in ‘effective occupation’. This meant that before taking formal control, an economic influence had to be established in the region by private investors and entrepreneurs. For example, a noted ‘man on the spot’ was Cecil Rhodes. At the age of seventeen Rhodes went to Arica and became a multimillionaire through diamond and gold mining enterprises. In 1889 he founded the British South Africa Company and used this organization to push British control northwards from Cape Colony to establish Rhodesia, a colony named after himself. The role of the individual itself was of limited importance in driving or furthering British expansion into Africa as few entrepreneurs managed o push forward territory as Rhodes had. However, it was ultimately motivated by economic interests and it allowed the British government to most significantly protect British influence in an area by proving ‘effective occupation’ which therefore allowed Britain to compete in the scramble with other nations and thereby protect its trade and economic interests in Africa. Finally, of foremost importance in motivating British expansion into Africa was the economic interest the continent held for Britain. Firstly Britain’s colonies along the west coast had always been strategically important for the vital trade route to India and later North Africa became equally as vital in Britain’s route to India via the Suez Canal. However, beyond this Britain was extremely keen to exploit the continents abundance of natural materials and extremely valuable minerals. This is evident as Britain was clearly only interested in seizing colonies that, if not strategically important, were rich in materials to exploit. For example, Egypt was seized by Britain due to its vast economic importance as it provided the quick route to India and additionally produced high quality cotton which was much sought after by British textile manufacturers. Furthermore the attraction to the British of Nigeria lay in the palm oil trade as palm oil was used in the manufacture of soap and candles and as an industrial lubricant. Britain also saw great potential for trade in East Africa; Zanzibar imported significant quantities of manufactured goods from Britain and India. It was a major trading point from which came ivory and leather goods and into which went textiles, brass and steel from Britain. Britain’s primary interest was trade and economic gain. Without any economic potential in an area Britain was not interested in colonization, in contrast if a region held great economic investments, for example Egypt, Britain was quick to occupy the area despite its reluctance to extend formal control which it viewed as consuming time, people and money. In summary, Africa’s economic potential was clearly the primary reason for British expansion into Africa 1868-1902. Britain was not a solely altruistic nation which became involved in the continent purely to help the people, instead it was driven by its own gains. It is true that rivalry from other great European powers was vital in turning British control in Africa from informal into solid occupation, however essentially Britain’s determination not to allow other nations to grab land was to avoid threat to its trade and economic interests in a region. Moreover, Africa’s strategic importance was also highly valued by Britain, yet once again its ultimate value lay in its path along the crucial route to India and therefore the protection of Britain’s economic interest.

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