Transport of Ions and Molecules Through the Cell Membrane

Differences between the intracellular and the extracellular fluid is brought about by transport mechanisms of cell membranes.

Extracellular fluid has a high sodium concentration and low potassium concentration.
Extracellular fluid contains a high chloride concentration
The concentration of phosphates and proteins in intracellular fluid are greater than those in extracellular fluid.

The cell membrane consists of a lipid bilayer with "floating" protein molecules. This is a barrier for most water-soluble substances. Lipid soluble substances can pass through the lipid bilayer. Protein molecules in the lipid bilayer form an alternative transport pathway:

Channel proteins: a watery pathway for molecules to pass through them

Carrier proteins: bind with specific molecules then undergo conformation changes that move molecules through the membranes.

Transport through the cell membrane occurs through diffusion or active transport.

Diffusion means random movement of molecules. Driven by normal kinetic energy of matter.

Active transport. Movement of substances across the membrane against the electrochemical gradient. This requires additional energy.

Diffusion is the continual movement of molecules in liquids or in gases. There are two types:

Simple diffusion: movement without binding to carrier proteins. Through the interstices of lipid bilayer, and through the water channels of transport proteins.

Facilitated diffusion: requires a carrier protein. Facilitates the passage through the membrane.

The rate of diffusion of a substance through the cell membrane is directly proportional to its lipid solubility. Oxygen, nitrogen carbon dioxide and alcohols are highly soluble.
Water and other lipid insoluble molecules diffuse through protein channels in the cell membrane.
Protein channels have selective permeability for transport of one or more specific molecules.

Gating of protein channels provides a means of controlling their permeability. Gating of the transport protein are Controlled in two ways:
Voltage gating : molecular conformation responds to electrical potential across the cell membrane. The gating of sodium channels or pores is the basic cause of action potentials in nerves.
Chemical gating the binding of a chemical on the transport channel changes its conformation and allows the opening or closing of the channel. The effect of acetylcholine on the acetylcholine channel.

Facilitated diffusion is also called carrier-mediated diffusion. There are 2 steps:
The molecule enters a channel and binds to a specific receptor.
Conformation change occurs in the carrier protein and the channel now opens to the opposite side of the membrane.
The rate of simple diffusion increases proportionately with the concentration of the diffusing substance.
Facilitated diffusion: The rate of diffusion approaches maximum with the as the concentration of the substance increases. This is limited to the maximum rate that the carrier protein will undergo conformational change.
Glucose and most of the amino acids undergo facilitated diffusion

Factors that affect the net rate of diffusion.
Substances can diffuse in both directions through the cell membrane. The net rate of diffusion in important in the desired direction. This is affected by:

Permeability: the net rate of diffusion of a substance through each unit area of the membrane for a unit concentration difference between the two sides of the membrane (when there is no electrical or pressure differences).
Concentration difference: The net rate of diffusion is proportionate to the difference in concentration of the diffusing substance on the two sides of the membrane.
Electronic potential: In response to the electrical potential across a membrane, the ions will move through the membrane because of their electrical charges. The concentration difference and the electronic potential difference are in balance - nernst equation

Expression
The two (ultimately equivalent) equations for these two cases (half-cell, full cell) are as follows:
$E_\text{red} = E^{\ominus}_\text{red} - \frac{RT}{zF} \ln\frac{a_\text{Red}}{a_\text{Ox}}$ (half-cell reduction potential)
$E_\text{cell} = E^{\ominus}_\text{cell} - \frac{RT}{zF} \ln Q$ (total cell potential)
where
E_red is the half-cell reduction potential at the temperature of interest

E^o_red is the standard half-cell reduction potential

E_cell is the cell potential (electromotive force)

E^o_cell is the standard cell potential at the temperature of interest

R is the universal gas constant: R = 8.314 472(15) J K⁻¹ mol⁻¹

T is the absolute temperature

a is the chemical activity for the relevant species, where a_Red is the reductant and a_Ox is the oxidant. a_X = γ_Xc_X, where γ_X is the activity coefficient of species X. (Since activity coefficients tend to unity at low concentrations, activities in the Nernst equation are frequently replaced by simple concentrations.)

F is the Faraday constant, the number of coulombs per mole of electrons: F = 9.648 533 99(24)×10⁴ C mol⁻¹

z is the number of moles of electrons transferred in the cell reaction or half-reaction

Q is the reaction quotient.

Nernst potential
Main article: Reversal potential
The Nernst equation has a physiological application when used to calculate the potential of an ion of charge z across a membrane. This potential is determined using the concentration of the ion both inside and outside the cell:
$E = \frac{R T}{z F} \ln\frac{[\text{ion outside cell}]}{[\text{ion inside cell}]} = 2.303\frac{R T}{z F} \log_{10}\frac{[\text{ion outside cell}]}{[\text{ion inside cell}]}.$
When the membrane is in thermodynamic equilibrium (i.e., no net flux of ions), the membrane potential must be equal to the Nernst potential. However, in physiology, due to active ion pumps, the inside and outside of a cell are not in equilibrium. In this case, the resting potential can be determined from the Goldman equation:
$E_{m} = \frac{RT}{F} \ln{ \left( \frac{ \sum_{i}^{N} P_{M^{+}_{i}}[M^{+}_{i}]_\mathrm{out} + \sum_{j}^{M} P_{A^{-}_{j}}[A^{-}_{j}]_\mathrm{in}}{ \sum_{i}^{N} P_{M^{+}_{i}}[M^{+}_{i}]_\mathrm{in} + \sum_{j}^{M} P_{A^{-}_{j}}[A^{-}_{j}]_\mathrm{out}} \right) }$
$E m$ = The membrane potential (in volts, equivalent to joules per coulomb)

$P ion$ = the permeability for that ion (in meters per second)

$[i o n] out$ = the extracellular concentration of that ion (in moles per cubic meter, to match the other SI units)

$[i o n] in$ = the intracellular concentration of that ion (in moles per cubic meter)

$R$ = The ideal gas constant (joules per kelvin per mole)

$T$ = The temperature in kelvin

$F$ = Faraday's constant (coulombs per mole)

The potential across the cell membrane that exactly opposes net diffusion of a particular ion through the membrane is called the Nernst potential for that ion. As seen above, the magnitude of the Nernst potential is determined by the ratio of the concentrations of that specific ion on the two sides of the membrane. The greater this ratio the greater the tendency for the ion to diffuse in one direction, and therefore the greater the Nernst potential required to prevent the diffusion.

Osmosis Across Selectively Permeable Membranes - Net diffusion of water.
Osmosis is the process of net movement of water caused by a concentration difference of water. Volume of water is precisely balanced so that there is no net movement of water. The volume of the cell remains consistent. In the event of a concentration difference of water across a cell membrane - there is a net movement of water. The pressure required to stop osmosis is the osmotic pressure.

The osmotic pressure exerted by particles in a solution is determined by the number of particles per unit volume of fluid and not by the mass of the particles. (as the kinetic energy in the interstitial fluid is about the same for most molecules regardless of size). Concentration is important.
The osmole expresses concentration in terms of number of particles.

In chemistry, the osmole (Osm or osmol) is a non-SI unit of measurement that defines the number of moles of a chemical compound that contribute to a solution's osmotic pressure. The term comes from the phenomenon of osmosis, and is typically used for osmotically-active solutions. For example, a solution of 1 mol/L NaCl corresponds to an osmolarity of 2 osmol/L. The NaCl salt particle dissociates fully in water to become two separate particles: an Na⁺ ion and a Cl^- ion. Therefore, each mole of NaCl becomes two osmoles in solution. Similarly, a solution of 1 mol/L CaCl₂, gives a solution of 3 osmol/L (Ca²⁺ and 2 Cl^-).

ACTIVE TRANSPORT
Active transport can move a substance against an electrochemical gradient. Active transport is divided into two types according to the source of energy used to cause the transport. Both are dependent on the carrier protein that penetrate through the cell membrane.
Primary active transport: The energy is derived from the breakdown of ATP to ADP
Secondary active transport: The energy is derived from the stored energy from ionic concentration differences secondary to the primary active transport.

Primary Active Transport: Sodium-potassium pump

Primary active Transport:
The Sodium Potassium Pump transports sodium ions out of the cells and potassium ions into the cells. This pump is responsible for the sodium potassium difference across cell membranes and establishing the negative electrical potential inside the cell. Three sodium ions bind to the carrier protein on inside of the cell membrane and two potassium ions bind to the carrier protein to the outside of the cell membrane. The binding activate ATP-ase activation and this cleaves one molecule of ATP, splitting one high energy bond to form ADP - this released energy causes a conformation change in the carrier protein extruding sodium to the outside and the potassium to the inside.
The sodium potassium pump controls cell volume. The continual net loss of ions - 3 sodium's out and 2 potassium's in - creates an osmotic tendency to move water out of the cell. When the cell begins to swell it activates the sodium potassium pump.

Active transport saturates in the same way that facilitated diffusion saturates. When the concentration difference is small the rate increases in proportion to the concentration difference. At high concentrations, the rate of transport is limited by the rate of conformation changes can occur.

Secondary Active Transport:

Co-transport and counter co-transport are two forms of secondary active transport: Secondary to the concentration gradient of sodium and potassium across the cell membrane - to maintain equilibrium -

Co-transport: The diffusion energy of sodium pulls other substances along with the sodium in the SAME DIRECTION through the cell membrane using special carrier proteins.

Counter-transport The sodium and the substance to be transported move in opposite directions across the membrane, with the sodium always moving to the interior of the cell, using a carrier protein.

Glucose and amino acids can be transported into most cells through sodium co-transport. The transport carrier site has two binding sites on the outside of the cell membrane - one for the sodium and one for the glucose or amino acid. The concentration of sodium is high on the outside, providing energy for the transport. The transport protein only undergoes conformation change once the glucose or the amino acid bind to the co-transporter.

Calcium and hydrogen ions can be transported out of the cells through the sodium counter-transport mechanism.

Calcium counter transport occurs in most cells with calcium moving out of the cell and sodium moving into the cell, both bound to the same transport protein.

Hydrogen counter-transport occurs especially in the proximal tubules of the kidneys, where the sodium ions move from the lumen to the tubule to the interior of the tubular cells and the hydrogen ions are counter-transported into the lumen

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Transport of Ions and Molecules Through the Cell Membrane

Expression

Nernst potential

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