Transport Across Cell Membrane Notes

Transport Through Cell Membrane Introduction

• All the cells in the body must be supplied with essential substances like nutrients, water, electrolytes, etc., and must get rid of many unwanted substances like waste materials, carbon dioxide, etc. The cells achieve these by means of transport mechanisms across the cell membrane.
• The structure of the cell membrane is well-suited for the transport of substances in and out of the cell. The lipids and the proteins of the cell membrane play an important role in the transport of various substances between ECF and ICF.

Read And Learn More: Medical Physiology Notes

Basic Mechanism Of Transport

Two types of basic mechanisms are involved in the transport of substances across the cell membrane:

1. Passive transport mechanism
2. Active transport mechanism.

1. Passive Transport:

• Passive transport is the transport of substances along the concentration gradient or electrical gradient or both (electrochemical gradient). It is also known as diffusion or downhill movement. It does not need energy. Passive transport is like swimming in the direction of water flow in a river.
• Here, the substances move from the region of higher concentration to the region of lower concentration. Diffusion is of two types namely, simple diffusion and facilitated diffusion.
• Simple diffusion of substances occurs either through the lipid layer or protein layer of the cell membrane. The facilitated diffusion occurs with the help of the carrier proteins of the cell membrane. Thus, the diffusion can be discussed under three headings:

1. 1. Simple diffusion through the lipid layer
   2. Simple diffusion through the protein layer
   3. Facilitated or carrier-mediated diffusion.

1. Simple Diffusion Through Lipid Layer: The lipid layer of the cell membrane is permeable only to lipid-soluble substances like oxygen, carbon dioxide, and alcohol. The diffusion through the lipid layer is directly proportional to the solubility of the substances in lipids.

2. Simple Diffusion Through Protein Layer: The protein layer of the cell membrane is permeable to water-soluble substances. Mainly electrolytes diffuse through the protein layer.

• Protein Channels or lon Channels:
  • Throughout the central lipid layer of the cell membrane, there are some pores. The integral protein molecules of the protein layer invaginate into these pores from either surface of the cell membrane. Thus, the pores present in the central lipid layer are entirely lined up by the integral Transport through Cell Membrane 27 protein molecules.
  • These pores are hypothetical pores and form the channels for the diffusion of water, electrolytes, and other substances, which cannot pass through the lipid layer. As the channels are lined by protein molecules, these are called protein channels for water-soluble substances.
• Types of Protein Channels or lon Channels:
  • The characteristic feature of the protein channels is selective permeability. That is, each channel can permit only one type of ion to pass through it.
  • Accordingly, the channels are named after the ions which diffuse through these channels such as sodium channels, potassium channels, etc.
• Regulation of the Channels: Some of the protein channels are continuously opened, and most of the channels are always closed. Continuously opened channels are called ungated channels. The closed channels are called gated. These channels are opened only when required.
• Gated Channels: The gated channels are divided into three categories:

1. Voltage-gated channels
2. Ligand-gated channels
3. Mechanically gated channels.

1. Voltage-gated channels:

• Voltage-gated channels are the channels which open whenever there is a change in the electrical potential. For example, in the neuromuscular junction, when an action potential reaches the axon terminal, the calcium channels are opened and calcium ions diffuse into the interior of the axon terminal from ECF.
• Similarly in the muscle, during the excitation-contraction coupling, the action potential spreads through the transverse tubules of the sarcotubular system. When the action potential reaches the cisternae, a large number of calcium ions diffuse from the cisternae into the sarcoplasm.

2. Ligand-gated channels:

• Ligand-gated channels are the type of channels which open in the presence of some hormonal substances. The hormonal substances are called ligands and the channels are called ligand-gated channels. During the transmission of impulse through the neuromuscular junction, acetylcholine is released from the vesicles.
• The acetylcholine moves through the presynaptic membrane (membrane of the axon terminal) and reaches the synaptic cleft. Then, the acetylcholine molecules cause the opening of sodium channels in the postsynaptic membrane and sodium ions diffuse into the neuromuscular junction from ECF.

3. Mechanically gated channels:

• Mechanically gated channels are the channels which are opened by some mechanical factors. Examples are the channels present in the pressure receptors (Pacinian corpuscles) and the receptor cells (hair cells) of the organ of Corti and the vestibular apparatus.
• When a Pacinian corpuscle is subjected to pressure, it is compressed resulting in deformation of its core fiber. This deformation causes the opening of the sodium channel and the development of receptor potential.
• The sound waves cause the movement of cilia of hair cells in the organ of Corti (cochlea) which is the receptor organ in the ear. The movements of the cilia cause the opening of potassium channels leading to the development of receptor potential. A similar mechanism prevails in hair cells of the vestibular apparatus also.

Facilitated Or Carrier Mediated Diffusion:

• Facilitated or carrier-mediated diffusion is the type of diffusion by which the water-soluble substances having larger molecules are transported through the cell membrane with the help of a carrier protein. By this process, the substances are transported across the cell membrane faster than the transport by simple diffusion.

• Glucose and amino acids are transported by facilitated diffusion. Glucose or amino acid molecules cannot diffuse through the channels, because the diameter of these molecules is larger than the diameter of the channels.
• The molecule of these substances binds with a carrier protein. Now, some conformational change occurs in the carrier protein. Due to this change, the molecule reaches the other side of the cell membrane.

Factors Affecting Rate Of Diffusion: The rate of diffusion of substances through the cell membrane is affected by the following factors:

• Permeability of the Cell Membrane: The rate of diffusion is directly proportional to the permeability of the cell membrane. Since the cell membrane is selectively permeable, only a limited number of substances can diffuse through the membrane.
• Temperature: The rate of diffusion is directly proportional to the body temperature. A slight increase in temperature increases the rate of diffusion. This is because of the thermal motion of the molecules during increased temperature.
• Concentration Gradient or Electrical Gradient of the Substance across the Cell Membrane: The rate of diffusion is directly proportional to the concentration gradient or electrical gradient of the diffusing substances across the cell membrane. However, facilitated diffusion has some limitations beyond a certain level of concentration gradient.
• Solubility of the Substance: The diffusion rate is directly proportional to the solubility of substances, particularly lipid-soluble substances. Since oxygen is highly soluble in lipids it diffuses very rapidly through the lipid layer.
• The thickness of the Cell Membrane: The rate of diffusion is inversely proportional to the thickness of the cell membrane. If the cell membrane is thick, the diffusion of the substances is very slow.
• Size of the Molecules: The rate of diffusion is inversely proportional to the size of the molecules. Thus, the substances with smaller molecules diffuse more rapidly than the substances with larger molecules.
• Size of the loans:
  • Generally, the rate of diffusion is inversely proportional to the size of the ions. Smaller ions can pass through the membrane more easily than larger ions with the same charge. However, it is not applicable always. For instance, sodium ions are smaller in size than potassium ions.
  • Still, sodium ions cannot pass through the membrane as easily as potassium ions because sodium ions have got the tendency to gather water molecules around them. This makes it difficult for sodium ions to diffuse through the membrane.
• Charge of the lons: The rate of diffusion is inversely proportional to the charge of the ions. The greater the charge of the ions, the lesser is the rate of diffusion. For example, diffusion of calcium (Ca++) ions is slower than that sodium (Na+) ions.

Special Types Of Passive Transport

In addition to diffusion, there are some special types of passive transport, viz.

1. Bulk flow
2. Filtration
3. Osmosis

1. Bulk Flow:

• Bulk flow is the diffusion of a large quantity of substances from a region of high pressure to a region of low pressure. Bulk flow is due to the pressure gradient across the cell membrane and the best example of this is the exchange of gases across the respiratory membrane in the lungs.
• The partial pressure of oxygen is greater in the alveolar air than in the alveolar capillary blood. So, oxygen moves from alveolar air into the blood through the respiratory membrane. The partial pressure of carbon dioxide is more in the blood than in the alveoli. So, it moves from the blood into the alveoli through the respiratory membrane.

2. Filtration:

• The movement of water and solutes from an area of high hydrostatic pressure to an area of low hydrostatic pressure is called filtration. The hydrostatic pressure is developed by the weight of the fluid.
• The filtration process is seen at the arterial end of the capillaries where the movement of fluid occurs along with dissolved substances from blood into the interstitial fluid. It also occurs in the glomeruli of the kidneys.

3. Osmosis:

• Osmosis is a special type of diffusion. It is defined as the movement of water or any other solvent from an area of lower concentration to an area of higher concentration of a solute through a semipermeable membrane.

• The semipermeable membrane permits the passage of only water or other solvents but not solutes. Osmosis can occur whenever there is a difference in the solute concentration on either side of the membrane.
• Osmosis across the cell membrane is of two types:

1.  Endosmosis movement of water into the cell
2.  Exosmosis movement of water out of the cell. Osmosis depends upon osmotic pressure.

• Osmotic Pressure:
  • Osmotic pressure is the pressure created by the solutes in a fluid. During osmosis, when water or any other solvent moves from an area of lower concentration to an area of higher concentration, the solutes in an area of higher concentration get dissolved in the solvent.
  • This creates pressure which is known as osmotic pressure. Normally, the osmotic pressure prevents further movement of water or other solvent during osmosis.
• Reverse Osmotic Pressure: It is a process in which water or other solvent flows in the reverse direction (from the area of higher concentration to the area of lower concentration of the solute) if an external pressure is applied on the area of higher
  concentration.
• Colloidal Osmotic Pressure and Oncotic Pressure: The osmotic pressure exerted by the colloidal substances in the body is called colloidal osmotic pressure. And, the osmotic pressure exerted by the colloidal substances (proteins) of the plasma is known as oncotic pressure and it is about 25 mm Hg.

Active Transport

Active transport is the movement of substances against the chemical or electrical or electrochemical gradient. It is like swimming against the water tide in a river. It is also called uphill transport. Active transport requires energy. The energy is obtained mainly by the breakdown of high-energy compounds like ATP.

• Active Transport vs Facilitated Diffusion: The active transport mechanism is different from facilitated diffusion by two ways:
  • The carrier protein of active transport needs energy whereas the carrier protein of facilitated diffusion does not need energy.
  • In active transport, the substances are transported against the concentration or electrical or electrochemical gradient. In facilitated diffusion, the sub-stances are transported along the concentration or electrical or electrochemical gradient.
• Uniport and Symport: In active transport, each carrier protein can carry one or more than one substances across the cell membrane. The carrier protein transporting only one substance is called a uniport or uniport pump. And the protein carrying more than one substance is called a symport or antiport pump (see below).

Mechanism Of Active Transport:

When a substance to be transported across the cell membrane comes near the cell, it combines with the carrier protein of the cell membrane and forms substance- protein complex. This complex moves towards the inner surface of the cell membrane.

Now, the substance is released from the carrier proteins. The same carrier protein moves back to the outer surface of the cell membrane to transport another molecule of the substance.

Substances Transported By Active Transport: The substances, which are transported actively, are in ionic form and nonionic form. The substances in the ionic form are sodium, potassium, calcium, hydrogen, chloride, and iodide. The substances in the nonionic form are glucose, amino acids, and urea.

Types Of Active Transport: Active transport is of two types:

1. Primary active transport
2. Secondary active transport

1. Primary Active Transport: Primary active transport is the type of transport mechanism in which the energy is liberated directly from the breakdown of ATP. By this method, the substances like sodium, potassium, calcium, hydrogen, and chloride are transported across the cell membrane.

• Primary Active Transport of Sodium and Potassium: Sodium-Potassium Pump:
  • Sodium and potassium ions are transported across the cell membrane by means of a common carrier protein called sodium-potassium (Na+ – K) pump. It is also called Na+-K+ ATPase pump or Na+ – K+ ATPase. This pump transports sodium from inside to outside the cell and potassium from outside to inside the cell. This pump is present in all the cells of the body.
  • Na+- K+ pump is responsible for the distribution of sodium and potassium ions across the cell membrane and the development of resting membrane potential.
• Structure of Na-K+ pump: The carrier protein that constitutes Na+ – K+ pump is made up of two protein subunit molecules: a subunit with a molecular weight of 100,000 and a β subunit with a molecular weight of 55,000. Transport of Na+ and K+ occurs only by the α subunit. The β subunit is a glycoprotein the function of which is not clear.
• α subunit of the Nat- K+ pump has got six sites:
  • Three receptor sites for sodium ions on the inner (towards cytoplasm) surface of the protein molecule
  • Two receptor sites for potassium ions on the outer (towards ECF) surface of the protein molecule
  • One site for the enzyme adenosine triphosphatase (ATPase), is near the sites for sodium.
• Mechanism of action of Na K+ pump:
  • Three sodium ions from the cell get attached to the receptor sites of sodium ions on the inner surface of the carrier protein. Two potassium ions outside the cell bind to the receptor sites of potassium ions located on the outer surface of the carrier protein.
  • The binding of the sodium and potassium ions to the carrier protein immediately activates the enzyme ATPase. ATPase causes the breakdown of ATP into ADP with the release of one high-energy phosphate. Now, the energy liberated causes some sort of conformational change in the molecule of the carrier protein.
  • Because of this, the outer surface of the molecule (with potassium ions) now faces the inner side of the cell. And, the inner surface of the protein molecule (with sodium ions) faces the outer side of the cell.
  • Now, dissociation and release of the ions take place so that the sodium ions are released outside the cell and the potassium ions are released inside the cell. The exact mechanisms involved in the dissociation and the release of the ions are not yet known.
• Electrogenic activity of Na+ – K+ pump:
  • The Na+-K+ pump moves three sodium ions outside the cell and two potassium ions inside the cell. Thus, when the pump works once, there is a net loss of one positively charged ion from the cell.
  • The continuous activity of these sodium-potassium pumps causes a reduction in the number of positively charged ions inside the cell leading to an increase in the negativity inside the cell. This is called the electrogenic activity of the Na+- K+ pump.

Transport of Calcium lons:

• Calcium is actively transported from inside to outside the cell by a calcium pump. The calcium pump is operated by a separate carrier protein. The energy is obtained from ATP by the catalytic activity of ATPase.
• Calcium pumps are also present in some organelles of the cell such as the sarcoplasmic reticulum in the muscle and the mitochondria of all the cells. These pumps move calcium into the organelles.

Transport of Hydrogen lons:

The hydrogen ion is actively transported across the cell membrane by the carrier protein called the hydrogen pump. It also obtains energy from ATP by the activity of ATPase. The hydrogen pumps that are present in two important organs have some functional significance.

1. Stomach: Hydrogen pumps in parietal cells of the gastric glands are involved in the formation of hydrochloric acid
2. Kidney: Hydrogen pumps in epithelial cells of distal convoluted tubules and collecting ducts are involved in the secretion of hydrogen ions from blood into urine.

2. Secondary Active Transport:

Secondary active transport is the transport of a sub-stance with sodium ion by means of a common carrier protein. When sodium is transported by a carrier protein, another substance is also transported by the same protein simultaneously, either in the same direction (of sodium movement) or in the opposite direction. Thus, the transport of sodium is coupled with the transport of another substance.

The secondary active transport is of two types:

1. Co-transport
2. Counter transport.

• Symport and Antiport:
  • Symport is the carrier protein that transports two different molecules in the same direction across the cell membrane. It is also called a symport pump.
  • Antiport is the carrier protein that transports two different ions or molecules in opposite directions across the cell membrane. It is also called an antiport pump. Separate carrier proteins operate for each type.
• Sodium Co-transport:
  • It is the process in which along with sodium, another substance is transported by a carrier protein called symport. The energy released by the movement of sodium is utilized for the movement of another substance.
  • Substances carried by sodium co-transport: Glucose, amino acids, chloride, iodine, iron and urate.
    • Carrier protein for sodium co-transport:
      • The carrier protein for the sodium co-transport has two receptor sites on the outer surface.
      • Among the two sites, one is for the binding of sodium and another site is for the binding of other substances.
    • Sodium co-transport of glucose:
      • One sodium ion and one glucose molecule from the ECF bind with the respective receptor sites of the carrier protein of the cell membrane. Now, the carrier protein is activated. It causes conformational changes in the carrier protein so that sodium and glucose are released into the cell.
      • Sodium co-transport of glucose occurs during the absorption of glucose from the intestine and reabsorption of glucose from the renal tubule.
    • Sodium co-transport of amino acids:
      • The carrier proteins for the transport of amino acids are different from the carrier proteins for the transport of glucose. For the transport of amino acids, there are five sets of carrier proteins in the cell membrane.
      • Each one carries different amino acids depending upon the molecular weight of the amino acids.
      • The sodium co-transport of amino acids also occurs during the absorption of amino acids from the intestine and reabsorption from the renal tubule.
    • Sodium Counter Transport: It is the process by which the substances are transported across the cell membrane in exchange for sodium ions by the carrier protein called antiport. The various counter-transport systems are:
      1. Sodium-calcium counter transport: In this, sodium and calcium ions move in opposite directions with the help of a carrier protein. This type of transport of sodium and calcium ions is present in all the cells.
      2. Sodium-hydrogen counter transport: In this system, the hydrogen ions are exchanged for sodium ions and this occurs in the renal tubular cells. The sodium ions move from the tubular lumen into the tubular cells and the hydrogen ions move from the tubular cell into the lumen.
      3. Other counter-transport systems: The other counter-transport systems are sodium-magnesium counter transport, sodium-potassium counter transport, calcium-magnesium counter transport, calcium-potassium counter transport, chloride-bicarbonate counter transport, and chloride-sulfate counter transport.

Special Types Of Active Transport

In addition to primary and secondary active transport systems, there are some special categories of active transport which are generally called vesicular transport.

Special categories of active transport are:

1. Endocytosis
2. Exocytosis
3. Transcytosis

1. Endocytosis: Endocytosis is defined as a transport mechanism by which the macromolecules enter the cell. The macro-molecules (substances with larger molecules) cannot pass through the cell membrane either by active or by passive transport mechanism. Such substances are transported into the cell by endocytosis.

Endocytosis is of three types:

1. Pinocytosis
2. Phagocytosis
3. Receptor-mediated endocytosis.

1. Pinocytosis: Pinocytosis is a process by which macromolecules like bacteria and antigens are taken into the cells. It is otherwise called cell drinking.

• Mechanism of pinocytosis:
  • Pinocytosis involves the following events:
    • The macromolecules (in the form of droplets of fluid) bind to the outer surface of the cell membrane
    • Now, the cell membrane evaginates around the droplets
    • The droplets are engulfed by the membrane
    • The engulfed droplets are converted into vesicles and vacuoles, which are called endosomes
    • The endosome travels into the interior of the cell
    • The primary lysosome in the cytoplasm fuses with the endosome and forms the secondary lysosome vii. Now, hydrolytic enzymes present in the secondary lysosome are activated resulting in digestion and degradation of the endosomal contents.

2. Phagocytosis:

• Phagocytosis is the process by which particles larger than the macromolecules are engulfed into the cells. It is also called cell eating. Larger bacteria, larger antigens, and other larger foreign bodies are taken inside the cell by means of phagocytosis.
• Only a few cells in the body like neutrophils, monocytes, and tissue macrophages show phagocytosis. Among these cells, the macrophages are the largest phagocytic cells.

Mechanism of phagocytosis:

• When the bacteria or the foreign body enters the body, first the phagocytic cell sends cytoplasmic extension (pseudopodium) around the bacteria or the foreign body
• Then, these particles are engulfed and are converted into endosomes like vacuoles. The vacuole is very large and it is usually called the phagosome
• The phagosome travels into the interior of the cell iv. The primary lysosome fuses with this phagosome and forms a secondary lysosome
• The hydrolytic enzymes present in the secondary lysosome are activated resulting in digestion and degradation of the phagosomal contents.

3. Receptor-Mediated Endocytosis: It is the transport of macromolecules with the help of a receptor protein. The surface of the cell membrane has some pits which contain a receptor protein called clathrin. Together with a receptor protein (clathrin), each pit is called a receptor-coated pit. These receptor coated pits are involved in receptor-mediated endocytosis.

• Mechanism of receptor-mediated endocytosis:
  • The receptor-mediated endocytosis is induced by substances like ligands.
  • The ligand molecules approach the cell and bind to the receptors in the coated pits and form the ligand-receptor complex
  • The ligand-receptor complex gets aggregated in the coated pits. Then, the pit is detached from the cell membrane and becomes the coated vesicle. This coated vesicle forms the endosome
  • The endosome travels into the interior of the cell. The primary lysosome in the cytoplasm fuses with the endosome and forms the secondary lysosome
  • Now, the hydrolytic enzymes present in the secondary lysosome are activated resulting in the release of the ligands into the cytoplasm
  • The receptor may move to a new pit of the cell membrane.

Receptor-mediated endocytosis plays an important role in the transport of several types of macromolecules into the cells, viz.

• Hormones: Growth hormone, thyroid stimulating hormone, luteinizing hormone, prolactin, insulin, glucagon, calcitonin, and catecholamines
• Lipids: Cholesterol and low-density lipoproteins (LDL)
• Growth factors (GF): Nerve GF, epidermal GF, platelet-derived GF, interferon
• Toxins and bacteria: Cholera toxin, diphtheria toxin, pseudomonas toxin, resin, and concanavalin A
• Viruses: Rous sarcoma virus, stemlike forest virus, vesicular stomatitis virus and adenovirus
• Transport proteins: Transferin and transcobalamin
• Antibodies: IgE, Polymeric IgG, and Maternal IgG. Some of the receptor-coated pits in the cell membrane are coated with another protein called caveolin instead of clathrin. The caveolin-coated pits are concerned with the transport of vitamins into the cell

2. Exocytosis: Exocytosis is the process by which substances are expelled from the cell. In this process, the substances are extruded from the cell without passing through the cell membrane. This is the reverse of endocytosis.

• Mechanism of exocytosis:
  • Exocytosis is involved in the release of secretory substances from the cells. The secretory substances of the cell are stored in the form of secretory vesicles in the cytoplasm. When required, the vesicles approach the cell membrane and get fused with the cell membrane.
  • Later, the contents of the vesicles are released out of the cell. Calcium ions play an important role during the release of some secretory substances such as neurotransmitters. The calcium ions enter the cell and cause exocytosis. However, the exact mechanism of exocytosis is not clear.

3. Transcytosis: Transcytosis is a transport mechanism in which an extracellular macromolecule enters through one side of a cell, migrates across the cytoplasm of the cell, and exits through the other side.

• Mechanism of transcytosis: The cell encloses the extracellular substance by invagination of the cell membrane to form a vesicle. The vesicle then moves across the cell and is thrown out through the opposite cell membrane by means of exocytosis.

Molecular Motors

Molecular motors are protein-based molecular machines that perform intracellular movements in response to specific stimull.

The examples of molecular motors are:

• Motor proteins like myosin, kinesin and dynein
• Polymerases like DNA polymerase and RNA poly- merase
• Actin
• ATP synthetase
• Topoisomerase

Applied Physiology

Abnormalities of Na’ – K Pump: Abnormalities in the number or function of Na+-K+ pump are associated with several pathological conditions. Important examples are:

• Reduction in either the number or concentration of Na+- K+ pump In myocardium is associated with cardiac failure
• Excess reabsorption of sodium in renal tubules is associated with hypertension.

Ion Channel Diseases: Mutations in genes that encode the ion channels cause some diseases.

• Sodium channel diseases: Muscle spasms and Liddle’s syndrome (dysfunction of sodium channels in the kidney resulting in increased osmotic pressure in the blood and hypertension).
• Potassium channel diseases: Disorders of heart, Inherited deafness and epileptic seizures in newborn.
• Chloride channel diseases: Renal stones and cystic fibrosis are generalized disorders affecting the functions of many organs such as lungs (due to excessive mucus), exocrine glands like the pancreas, biliary system, and immune system.