Transport across cell membrane is classified into four ways: 1. Diffusion (Passive Transport) 2. Osmosis 3. Active Transport 4. Vesicular Transport.
Cell membrane acts as a barrier to most, but not all molecules. Cell membranes are semi-permeable barrier separating the inner cellular environment from the outer cellular environment. Since the cell membrane is made up of a lipid bilayer with proteins attached on the surface and also passing through the cell membrane, there is possibility of transport across this membrane.
All lipid soluble substances can easily and freely diffuse in and out, e.g. O2 and CO2. Whereas water soluble substances like ions, glucose and macromolecules should find a special way of transport with the help of integral and trans-membrane proteins which act as binding sites, channels and gates to facilitate movement.
Way # 1. Diffusion (Passive Transport):
It is the net movement of a substance (liquid or gas) from an area of higher concentration to lower concentration without expenditure of energy is called diffusion.
Diffusion can be further divided as follows:
A. Simple diffusion
B. Facilitated diffusion.
A. Simple Diffusion:
It is further classified into two categories:
i. Diffusion of lipid soluble substance through lipid bilayer.
ii. Diffusion of lipid insoluble substance through protein channels.
i. Diffusion of Lipid Soluble Substance through the Lipid Bilayer:
Substance like oxygen and carbon dioxide and alcohols are highly lipid soluble and dissolve in the layer easily and diffuse through the membrane. The rate of diffusion is determined by the solubility of the substance. For example, exchange of gases in the lungs.
ii. Diffusion of Lipid Insoluble Substance through Protein Channels:
This is possible through either selective permeability of protein channel or through gated channels.
Selective Permeability of Protein Channel:
This channel can permit only one type of ion to pass through it. The selectivity is due to diameter, shape and electrical charges along the inner surface of the channel.
For example:
a. Sodium Channels:
Sodium channel is a tetramer with a pore of 0.3 to 0.5 nm in diameter which is selective for sodium. It has strong negative charge on the inner surface which allows dehydrated sodium ion to diffuse in either direction from higher to lower concentration.
b. Potassium Channels:
It is selective for potassium. The pore of this channel is smaller than sodium channel and is not negatively charged. But hydrated form of potassium ion is smaller in size than sodium and all thus allows selectively permits potassium ion to diffuse.
Diffusion through Gated Protein Channels:
A part of or projection from a protein channel behaves like a gate and can open or close in response to a change in voltage, ligand (chemical), mechanical stimuli like touch and stretch are called as voltage gated, ligand gated and mechanical gated channels respectively.
a. Voltage-Gated Channels:
These channels are open and close in response to change in electrical potential across the cell membrane.
Example:
Excitable cells like neurons and muscle cells. When the voltage across the membrane changes, the voltage-gated sodium channels open and allow flow of sodium ions into the cell which cause depolarization phase of action potential and outflow of potassium through voltage-gated potassium channel brings about repolarisation. This is basis of action potential in an excitable cell.
b. Ligand (Chemical) Gated Channel:
Some channels open in response to a chemical substance. They can be internal ligand, where binding side is on the cytosol side of channel. For example, second messengers. There can also be external ligand which binds to a site on the extracellular side of the channel.
Example:
Neurotransmitters like acetylcholine, gamma-amino butyric acid which transmits impulse in a synapse.
c. Mechanical-Gated Channels:
They respond to mechanical stimulus and the deformation due to mechanical stimulus opens or closes the channel.
Example:
Pressure receptors when subject to, pressure opens sodium channel and causes development of a receptor potential. This helps us to feel sense of pressure.
B. Facilitated Diffusion:
It is also called carrier mediated diffusion. Highly charged or big molecules which cannot pass through protein channels require carrier protein which facilitates the diffusion. The carrier protein is selective for that particular substance. When a substance to be transported binds to a carrier protein on one side there is conformational change in the shape of the protein which carries the substance to the interior of the cell by opening to other side of membrane. It also obeys the law of diffusion (higher to lower concentration).
Example:
Glucose transporters (GLUT) and amino acid transporters.
Factors that affect Net Rate of Diffusion:
Factors that is directly proportional to diffusion:
i. Concentration gradient across the membrane
ii. Electrical and pressure gradient across the membrane
iii. Solubility of the substance
iv. Body temperature
v. Permeability of cell membrane.
Factors that is inversely proportional to diffusion:
i. Thickness of cell membrane
ii. Size of ion/molecule.
Applied Physiology:
Local anaesthetics act directly on gates of the sodium channel, making it difficult to open and thereby reducing excitability of the cell. The impulse fails to travel causing anaesthesia.
Ion channel mutation is called as chanellopathies.
They affect muscle and brain tissue mainly:
i. Sodium channel disease:
Muscle spasm and Liddle’s syndrome.
ii. Potassium channel disease:
Arrhythmia, seizures in newborn and inherited deafness.
iii. Chloride channel disease:
Kidney stones and cystic fibrosis.
Way # 2. Osmosis:
Osmosis is net movement or diffusion of water molecules across a semipermeable membrane from a region of higher concentration to lower concentration of water (solvent) or in other words movement of water from a region of low concentration of solute (namely salts and electrolytes) to higher concentration of solute.
Osmotic Pressure:
If a pressure is applied to the sodium chloride solution, osmosis of water into the solution is stopped, reversed or slowed. The pressure required to stop osmosis is called as osmotic pressure. Osmotic pressure is determined by the number of particles per unit volume of fluid and not by the mass of the particle.
Osmolality and Osmolarity:
A mole is gram molecular weight of substance. One osmole is equal to gram molecular weight of a substance divided by the number of particles in a solution. So osmolarity is the number of osmoles per liter of a solution. Osmolality is the number of osmoles per kg of solvent. Osmotically active substance is dissolved in the body water, so osmolarity is expressed as milliosmoles (mOsm) per liter of water.
Colloid Osmotic Pressure:
It is the pressure exerted by the colloids present in the solution.
Oncotic Pressure:
The colloid osmotic pressure exerted by the plasma proteins is known as oncotic pressure.
Tonicity:
It is the used to describe the osmolality of a solution relative to plasma. If a solution has same osmolality or increased or decreased osmolality as plasma it is said to be isotonic, hypertonic and hypotonic solution respectively.
Applied Physiology:
Any solution used for fluid replacement, the tonicity of the solution has to be considered depending on the clinical situation.
Way # 3. Active Transport:
When a substance moves across the cell membrane against concentration or electrical gradient (uphill) with the expenditure of energy it is called active transport. The energy is obtained from the breakdown of high energy compounds like ATP.
They are classified as primary and secondary active transport according to the source of energy utilized. The transporter involved here is also carrier protein. But it is different from that in facilitated diffusion. Here the carrier protein is capable of imparting energy to the transported substance to move against gradient.
i. Primary Active Transport:
In the primary active transport, the energy is liberated directly from the break-down of ATP and the carrier protein involved here is called as pump. The enzymes which catalyze the hydrolysis of ATP are called ATPases. Hence these pumps are called as ATPases.
Sodium Potassium Pumps or Sodium Potassium ATPases:
Location:
Almost all cells have Na+ K+ pumps especially in all excitable cells.
Structure:
It has two subunits namely α and β sub-units.
Separation of subunit eliminates activity but the function of β subunit is unknown, α subunit has:
a. Three receptor sites for binding sodium ion on the protein that protrudes to the interior of the cell.
b. Two receptor sites of potassium ions on the outside of the cell.
c. One site of ATPase enzyme which is near to the binding site for sodium.
Mechanism of Action:
The function is to pump out excess Na+ from the intracellular fluid and to draw in K+ into the cell. Since there are 3 sites for Na+ and 2 sites for K+, the pump gets activated only when three Na+ ion and two K+ ion attaches to the interior and exterior surface of the cell respectively. For every three sodium ions expelled out of cell, two potassium ions are drawn in. Thus, there is a net loss of positive charge (ion) out of the cell, which initiates osmosis of water out of the cell as well as prevents any cell from swelling.
The above mechanism also creates positivity outside the cell but leaves a deficit of positive ions inside the cell. Therefore the Na+ K+ pump is said to be electrogenic because it creates an electrical potential across the cell membrane as it pumps. This is required for genesis of resting membrane potential (RMP) which is the membrane potential across the cell membrane at rest.
Functions:
i. It controls the volume of the cells
ii. Maintains resting membrane potential.
Applied Physiology:
Digitalis is a drug used in management of congestive cardiac failure. It inhibits sodium potassium pump. This causes increase in ICF sodium. This decreases calcium efflux through sodium calcium antiport by decreasing sodium influx. This finally increases calcium concentration in the myocardial cells which increases myocardial contractility.
Hydrogen Potassium ATPases:
Location:
Gastric glands of stomach and distal convoluted tubules of nephron.
Functions:
i. In parietal cells of the gastric glands it transports hydrogen ions. At the secretory end of these cells hydrogen is pumped into stomach along with chloride ions to form hydrochloric acid which is the main composition of gastric juice.
ii. Intercalated cells in the distal tubules of the nephron pump hydrogen ions for the formation of urine and controls pH in the body.
ii. Secondary Active Transport:
In some places, due to active transport of Na+ out of cells by Na+ K+ pump, a large concentration gradient of sodium usually develops with high concentration outside than inside. This gradient stores free energy which is used to transport other substances like glucose and amino acid and other ions against their concentration gradient. The energy spent is not directly due to hydrolysis of ATP but stored energy due to primary active transport.
Secondary active transport is of two types:
(a) Co-Transport,
(b) Counter Transport.
(a) Co-Transport:
It is otherwise called symport. Here sodium and other substance that is be transported moves in the same direction.
Example:
Sodium glucose co-transport in proximal convoluted tubule of nephron ― Here carrier protein undergoes conformational change and ready for transporting only when sodium and glucose attaches to it and both moves in same direction. The energy is obtained from the stored energy due to sodium transport by Na+ K+ pump on the basolateral membrane of the tubule. This creates a high concentration gradient for sodium ion inside the tubular cell. Thereby the stored energy due to the gradient is used for sodium as well as glucose transport along with it along the luminal side of the tubule.
(b) Counter Transport:
It is otherwise called antiport. Here sodium and other substances to be transported move in the opposite direction.
Example:
Sodium calcium antiport in myocardial cells.
Way # 4. Vesicular Transport:
They are classified as:
i. Vesicle transport within the cell
ii. Endocytosis
iii. Exocytosis
iv. Transcytosis
i. Vesicle Transport within the Cell:
Vesicles that help in transport of proteins from one organelle to the other within the cell have protein coats namely caveolin, clathrin 1, clathrin 2 and so on. These protein coats are specific for transport to specific organelle. A particular protein on vesicle will latch with its corresponding pair protein on the target so that vesicle makes sure that it docks to the correct destination. In general, vesicle move along microtubule motors like dynamin.
ii. Endocytosis:
Endocytosis and exocytosis can also be considered under vesicle transport because this type of transport occurs by forming vesicle. Endocytosis is a process by which substance are engulfed by the cells.
For example:
Bacteria and dead tissue engulfed by WBC.
Receptor Mediated Endocytosis:
Endocytosis can also be specific if it is receptor mediated called as receptor mediated endocytosis. Here the molecule or ligand attach to the specific receptor on the cell membrane, which are present in pits called clathrin pits on the cell membrane. Clathrin molecules have three legs radiating from a central point that surrounds the endocytic vesicle and is pinched off into the cytoplasm. Once vesicle is formed, clathrin falls off and reutilized. The vesicle then reaches the target.
Example:
Vitamins, transferrin and cholesterol entry into the cell.
Mechanism of Endocytosis:
Some mechanisms of endocytosis are:
1. Materials to be engulfed come in contact with the cell membrane.
2. Cell membrane invaginates along with the material
3. Invagination is pinched off into the cells
4. Pinched off material inside the cell forms a vesicle and leaving cell membrane intact―
a. If it is a solid material it is called phagocytosis (cell eating)
b. If it is a solution it is called as pinocytosis (cell drinking)
iii. Exocytosis:
It is a reverse pinocytosis where substances synthesized within the secretory cells are secreted out of the cell. The secretory vesicle moves to the inside of the cell membrane and fuses with them. The contents are extruded and vesicle membrane becomes a part of cell membrane. For example, release of neurotransmitters. Both endocytosis and exocytosis maintains cell membranes surface area.
iv. Transcytosis:
It is otherwise called as cytopempsis. The mechanism involves the endocytosis of the vesicle at one side of the membrane and exocytosis at the opposite side. The binding site of the vesicle has caveolin coated pits. For example, transport of nutrients across endothelial cells of blood vessels to the interstitial fluid.