Ligand & Voltage-Gated Ion Channels

• Ligand-gated ion channels convert chemical signals into electrical signals

Synapse Level

• A chemical signal, or neurotransmitter, binds to a receptor

• This connection triggers the opening of the ion channel.

• Ions then enter the cell.

• This leads to a change in membrane potential

• Voltage-gated Ca2+ channels transform electrical signals into chemical signals

Nerve Terminus Level

• An action potential induces the opening of voltage-gated Ca2+ channels

• This triggers Ca2+ entry.

• Ca2+ entry leads to the fusion of synaptic vesicles with the plasma membrane

• The neurotransmitter is then released into the synaptic cleft

• Membrane transport of small molecules can occur via simple diffusion or transport proteins without movements of the plasma membrane

• Macromolecules and particles require movements of the plasma membrane to be transported across it

Transport of Macromolecules

• The transport involves morphological modifications of the plasma membrane
• Vesicles are formed to enclose the transported products for transient transport
• Cellular materials are transported by endocytosis or exocytosis

Transport via Exocytosis

• Exocytosis involves the secretion or elimination of molecules from the cell, substances are enclosed in vesicles that fuse with the membrane to discharge their contents (waste, mucus, neurotransmitters, hormones) into the extracellular environment
• This mechanism allows the plasma membrane to grow larger.
• Exocytosis has two types: constitutive and induced

Constitutive Exocytosis

• This involves goblet cells of the intestine epithelium secrete mucopolysaccharides and glycoproteins of the glycocalyx constantly

Induced or Regulated Exocytosis

• Small simple molecules are actively transported to the lumen of secretory vesicles
• Vesicles accumulate and fuse with the membrane upon stimulation

Transport via Endocytosis

• Endocytosis is the process by which a cell takes up particles or solutes
• This done by encasing them in vesicles through invagination of the plasma membrane
• There are different types of endocytosis based on the substances ingested and their size: pinocytosis, receptor-mediated endocytosis, and phagocytosis

Phagocytosis

• Phagocytosis or "cell eating" involves bacteria and food
• Vacuoles form
• Fusion occurs with a lysosome
• Digestion of materials occurs in specialized cells such as macrophages and epithelial cells
• Molecules larger than 0.5µm such as bacteria and debris of dying cells, are phagocytized
• A bacterium's binding stimulates the extension of a pseudopodium, which engulfs it
• Fusion of the pseudopodium membranes results in the formation of a large intracellular vesicle (phagosome)
• Particles to be phagocytized bind to the plasma membrane via receptors like CAMs, SAMs, and the receptor of Fc fragment of antibodies that cover bacteria
• The hyaloplasm, with a large surface of the plasma membrane and the underlying cytoplasm disform with reorganization of the cytoskeleton in order to engulf the particle
• The phagosome merges with lysosomes to form a phagolysosome, where digestion takes place
• Pseudopods are formed by actin filaments
• Digestion can be blocked by microorganisms (e.g., Mycobacterium tuberculosis)
• Incomplete digestion leads to residual bodies undergoing exocytosis or storage in the membrane as lipofuscin granules, which could be symptomatic of membrane damage and aging of cells and organs

Pinocytosis

• Pinocytosis or "cell drinking" involves the uptake of dissolved materials through the use of small vesicles, with a diameter near 150 nm
• Tiny droplets of fluid are trapped by folds in the plasma membrane
• It's a non-specific uptake of volumes of culture medium with the glycocalyx playing a role

Receptor-Mediated Endocytosis

• Specific molecules combine with receptors on the plasma membrane, particularly useful for macromolecules
• This process increases internalization efficiency 1000 times
• Cholesterol uptake serves as an example: -Cholesterol is transported in the blood by LDL (low-density lipoproteins) or "bad cholesterol"
  • Cholesterol serves as a component of the cell membrane and as a precursor for steroid hormones
• Brown and Goldstein received the Nobel Prize in 1985 for their work on cholesterol receptors
• If cholesterol outside the cell (in the blood) cannot enter the cell, it deposits in the artery walls leading to cardiovascular diseases
• When a cell needs cholesterol, it produces LDL receptors
• Receptors are concentrated in coated pits, which are depressed regions on the cytoplasmic surface of the plasma membrane
• Each pit is coated by clathrin
• LDL acts as a ligand
• Ligands bind to receptors in coated pits of the plasma membrane, forming coated vesicles via endocytosis
• After vesicles detach from the membrane, the clathrin coat is removed with the help of HSP70 and ATP
• Coating detaches from the vesicle, uncoated vesicle fuses with endosome, ligands separate from receptors and are recycled; endosome fuses with primary lysosome, forming a secondary lysosome
• Contents of secondary lysosomes are digested and released into the cytosol
• The receptor returns to the plasma membrane through a vesicle

Potocytosis

• Potocytosis is a type of receptor-mediated endocytosis
• It involves small molecules transported across the plasma membrane of a cell
• Molecules are transported by caveolae instead of clathrin-coated vesicles, and deposited directly into the cytosol
• Potocytosis begins when an extracellular ligand binds to a receptor protein on the cell surface, initiating the formation of an endocytic vesicle
• The ligand typically has a low molecular mass (e.g., vitamins), but some larger molecules, such as lipids, can also act as ligands
• potocytosis includes membrane receptors deprived of cytoplasmic domains
• occurs in lipid rafts rich with cholesterol, sphingolipids and glangliolipids tightly connected to GPI receptors
• The receptors localized in the membrane of the vesicle (caveolae) are glycoproteins anchored by a glycosyl-phosphatidyl-inositol GPI to the extracellular leaflet of the lipid bilayer
• Caveoline (21 KDa) is an intrinsic protein synthesized by the RER
• The potocytosis vesicles do not fuse with endosomes or lysosomes, unlike classic endocytosis vesicles