Ion Transport Mechanisms and Cystic Fibrosis

• Cell membrane transport facilitates the movement of substances across the plasma membrane.

Cystic Fibrosis Disease

• Cystic fibrosis is a genetic disorder caused by a mutation in the gene encoding a chloride channel (Cl- channel).
• Malfunctioning chloride channels disrupt chloride ion transport across cell membranes, leading to thick, sticky mucus buildup in organs like the lungs and digestive system.

Transport Proteins

• Two main types of proteins, channels and transporters, are involved in transporting inorganic ions and small organic molecules across the plasma membrane.
• Channels form tiny hydrophilic pores allowing substances to pass by diffusion.
• Most channels are ion channels.
• Transporters transfer inorganic ions or small organic molecules and can be active or passive.

Ion Concentration and Membrane Potential

• Na+, K+, Ca2+, Cl-, and H+ (protons) are the most important inorganic ions for cells
• Ion concentrations inside and outside the cell differ greatly.
• Na+, Cl-, and Ca2+ are more abundant outside the cell, specifically Na+ is 10 times higher, Cl- is 14 times higher, and Ca2+ is 12 times higher.
• K+ is more abundant inside the cell, 25 times higher inside.
• Electrical charges inside and outside the cell are generally balanced (Na+ by Cl- and K+ by negatively charged organic molecules).
• Small charge differences exist across the plasma membrane, with more negative charges on the inner side
• The difference in charge is the membrane potential, measured in mV.

Electrochemical Gradient

• Molecules diffuse from areas of high concentration to low concentration
• Diffusion of inorganic ions or charged molecules depends on both concentration and charge differences (electrochemical gradient).

Ion Channels and Passive Transport

• Ion channels facilitate the diffusion of inorganic ions along their electrochemical gradient without requiring energy, called passive transport.

Ion Channel Selectivity

• Most channels in the cell are ion channels.
• Ion channels are narrow, highly selective, and facilitate the passage of specific inorganic ions.
• Ion channels are distinguished from pores by ion selectivity and open/closure state.
• A typical ion channel fluctuates between closed and open conformations

Gated Ion Channels

• A specific stimulus triggers gated-ion channels to switch between closed and open states.
• Voltage-gated ion channels are controlled by voltage changes across the membrane.
• Mechanically-gated ion channels are controlled by physical stimuli like light, sound, pressure, stretch, touch, and vibration.
• Ligand-gated ion channels are controlled by molecule binding.

Water Channels and Osmosis

• Osmosis is the diffusion of water across a membrane, from lower to higher solute concentration.
• Water molecules diffuse rapidly through aquaporin channels in the plasma membrane of cells in the nephron tissue.

Transporters

• Transporters change conformation to mediate transport across the membrane.
• Transporters can move one substance (uniporters) or two substances (symporters and antiporters) at a time.
• Active transporters use energy to move inorganic ions and small molecules against their electrochemical gradient.

Active Transporters

• Light, electrochemical gradients, and ATP are used to pump molecules against their concentration gradients within the cell.
• Bacteriorhodopsin, found in certain bacteria, uses light to pump protons from inside the cell to outside.
• Ca2+ transporters in the endoplasmic reticulum membrane maintain low cytosolic Ca2+ concentration; Ca2+ influx acts as an intracellular signal.
• ATP-driven Na+ transporters (Na+-K+ pump) use ATP energy to expel Na+ and bring in K+.
• Glucose-Na+ transporters use the electrochemical Na+ gradient to actively import glucose.
• Primary active transporters use ATP to create electrochemical gradients; secondary active transporters use these gradients for transport.

Active and Passive Transport in Glucose Transfer

• Glucose is actively taken up from the gut via Na+-driven glucose symport and passively released for use by other tissues.

Membrane Permeability

• Lipid bilayers are impermeable to most water-soluble molecules.
• A molecule's size and solubility determine its diffusion rate.

Substance Transport

• Substances cross the plasma membrane through simple diffusion, channels, passive transporters, or active transporters.

Cell Transporters

• Each cell membrane has its own characteristic set of transporters.

Endocytosis and Exocytosis

• Proteins, polysaccharides, and nucleic acids are too large/charged to pass through biological membranes, and utilize endocytosis/exocytosis.
• Insulin is secreted from pancreatic β cells via exocytosis.
• There are three types of endocytosis: receptor-mediated, pinocytosis, and phagocytosis.

Receptor-Mediated Endocytosis

• Receptor-mediated endocytosis is responsible for LDL uptake
• LDL (low density lipoprotein) transports cholesterol in the blood.
• LDL receptors on the cell surface bind LDL particles in the blood.
• Cholesterol is extracted from the LDL in the lysosome after endocytosis.

Phagocytosis

• Smaller cells and large particles are taken up by phagocytosis.