General Physiology Lecture 1

General Physiology - Lecture 1

• The lecture covers the physiology of the cell membrane, focusing on passive and active transport mechanisms.
• The topics include morphological and functional organization of the cell membrane, membrane lipids (structural and functional roles), membrane proteins (functional and structural roles), specialized structures of the cell membrane, transport functions, passive transport (diffusion, osmosis, filtration, ion channels), and active transport (primary active transport, secondary active transport).
• Learning objectives detail explaining the phospholipid matrix's role, membrane protein functions, passive and active transport characteristics, and the factors influencing transport rates.

Lecture Topics

• Morphological and functional organization of the cell membrane
• Membrane lipids: structural and functional roles (phospholipids, cholesterol, glycolipids)
• Membrane proteins: structural and functional roles (peripheral, integral)
• Specialized structures of the cell membrane: microvilli, intercellular junctions
• Transport functions of the cell membrane: passive and active transport
• Passive transport: diffusion, osmosis, filtration, ion channels
• Active transport: primary, secondary, types of ion pumps (Na+/K+, Ca2+, H+/K+ ,proton pumps)

Learning Objectives

• Explain the role of the phospholipid matrix in cell membrane permeability.
• Discuss classification criteria and functions of membrane proteins.
• Describe general classification criteria of membrane transport mechanisms.
• Define and describe characteristics of passive transport(diffusion and osmosis).
• List factors conditioning passive transport rates.
• Define and describe passive transport via ion channels (voltage-gated and ligand-operated).
• Define the characteristics of active transport through cell membranes.
• Describe the main types of ion pumps.
• Compare and contrast active and passive transport, and primary and secondary active transport.
• Describe the roles of Na+/K+ pump, Ca2+ pump, H+/K+ pump and proton pumps
• Discuss the role of active transport mechanisms in generating gradients.
• Discuss the importance of active transport in transmembrane exchanges (digestive and renal).

General Structure of the Cell

• The primary components of cells are the cell membrane, cytoplasm, and nucleus.
• The lecture provides an image with labeled cellular parts.

Morphological and Functional Organization of the Cell Membrane

• Cell membrane = plasmalemma
• Definition: a complex separating cells from the extracellular environment.
• Main function: a selective barrier controlling exchanges between cells and the extracellular environment.

Morphological and Functional Organization of the Cell Membrane: Structure and Function

• Structure: fluid lipoprotein mosaic model (Singer, Nicolson, 1972)
• Lipids: phospholipids, cholesterol, glycolipids.
• Proteins: peripheral, integral, glycoproteins.
• Specialized membrane structures: microvilli, intercellular junctions.

Membrane Lipids: Structural and Functional Role

• Phospholipids: form a bilayer, hydrophilic head, hydrophobic tail, hydrophobic core.
• Cholesterol: inner part, membrane stability and flexibility.
• Glycolipids: part of the glycocalyx, establishing contacts with the extracellular environment.

Functions of Phospholipid Matrix

• Membrane selective permeability: permeable to small lipophilic molecules (e.g., respiratory gases, fatty acids) impermeable to large, charged compounds, partially permeable to water.

Functions of Intracellular Messengers

• Phosphatidyl inositol-4,5-biphosphate (PIP2)
• Membrane C phospholipase → INTRACELLULAR MESSENGERS (e.g., IP3 and DAG)
• IP3 stimulates Ca2+ release and regulation of smooth muscle contraction.
• DAG activates membrane proteinkinase C and regulates cellular metabolism and secretion.

Functions of Extracellular Messengers

• Membrane phospholipids.
• Membrane A2 phospholipase → ARACHIDONIC ACID.
• Cyclooxygenase pathway → PROSTAGLANDINS (PGi2) - Vasodilation, inhibits platelets adherence and aggregation.
• Thromboxane (TxA2) – vasoconstriction, stimulates platelets adherence and aggregation.
• Lipoxygenase pathway → LEUKOTRIENES (LT). -Inflammation response, bronchial smooth muscle contraction.

Membrane Proteins: Functional and Structural Role

• Represent half of the membrane mass.
• Active element inducing membrane properties and functions.
• Classification: peripheral proteins (extrinsic), integral proteins (transmembrane, intrinsic).
• Peripheral proteins: mostly enzymes (acetylcholinesterase, adenylate cyclase).
• Integral proteins: cross the entire membrane (e.g., channel proteins, transporters, membrane receptors).

Membrane Proteins: Functional and Structural Role (Continued)

• Channel proteins: facilitate ion and water passage.
• Transporter proteins (carriers): transport specific molecules.
• Membrane receptors: bind to specific molecules.
• Intercellular attachment and recognition.
• Specialized structures of the membrane.
• Microvilli (increase absorption surface).
• Cilia and flagella (rhythmic movement and transport).
• Intercellular junctions: tight junctions, anchoring junctions (desmosomes).

Mechanisms of Passive Transport

• Diffusion (simple and facilitated).
• Osmosis.
• Filtration.
• Ion channels: leaky ion channels, gated ion channels.

Specialized Structures of the Membrane

• Tight junctions: impermeable junctions
• Roles: protection (prevent microorganisms), functional (connect apical poles, block integral protein movement).
• Desmosomes: anchoring junctions
• Gap junctions: connexons, allow bidirectional transfer.

Diffusion Transport Mechanisms

• Simple: movement through cell membrane (gas, water-soluble molecules).
• Facilitated: carrier protein needed (Glucose, amino acids).
• Ion channels.

Osmosis

• Net diffusion of water across a semipermeable membrane.
• Osmotic pressure gradient (Posm), controls water flow and permeability of particles.

Filtration

• Movement of water and small solutes across a membrane due to hydrostatic pressure differences.
• Pressure exerted by a fluid column on an exchange surface.

Membrane Ion Channels

• Integral membrane proteins.
• Based on channel dynamics: leaky ion channels, gated ion channels.
• Based on localization: plasma membrane channels, intracellular channels.

Voltage-Gated Ion Channels

• Channel dynamics: conformation changes.
• Types: fast Na+, K+, slow Ca2+, Cl- channels.

Fast Na+ Channels

• Distribution: neurons, skeletal muscle, myocardial fibers.
• Structural: strongly negatively charged, gates (activation and inactivation).
• Functional states: resting, activated, inactivated.
• Gates dynamics: critical for action potential generation.

K+ Channels

• Characteristics, structural and functional.

Slow Ca2+ Channels

• Characteristics, types, and roles (e.g., excitation-contraction coupling, cardiac automatism, exocytosis)

Cl- Channels

• Characteristics, location, and role (e.g., stabilizing resting potential, fine-tuning of cellular pH).

Ligand-Gated Ion Channels

• Channel dynamics: ligand binding at gate level.
• Types: extracellular and intracellular.

Intracellular Ligand-Gated Channels

• Location: membrane of epithelial cells or endoplasmic reticulum.
• Ligands: intracellular chemical/protein messengers.

Receptors-Operated Channels Through G Proteins

• Characteristics: Ca2+ or K+ channels, activation via G protein subunits.

Intercellular Channels (Connexons)

• Found at permeable junctions.
• Electrical synapses, permeability of molecules.
• Conductance suppression for regulation.

Active Transport

• Characteristics: movement against electrochemical gradient, energy required (ATP), specific transporter proteins (carriers).
• Types: primary active transport (directly using ATP), secondary active transport (using electrochemical gradient).

Primary Active Transport

• Characteristics: specific for ion transport.
• Types of ion pumps: Na+/K+ pump, H+/K+ pump, Ca2+ pump, proton pumps.

Ion Pumps

• Steps: ion binding, ATP binding and hydrolysis to change conformation of carrier protein, release of transported ion.

General Functions of Ion Pumps

• Provide electrochemical gradient of various substances, maintain ion balance for specific functions.

Na+/K+ Pump

• Characteristics: most important active transporters in cells, transports 3 Na+ out of cell and 2 K+ in , energy required.
• Structure: two a catalytic subunits, two β regulatory subunits.
• Functions: electronegative charge inside cell membrane for resting potential, restoration of ionic balance after repolarization, maintenance of cell volume.

Ca2+ Pump

• Characteristics: location (sarcolemma and SR level, SERCA).
• Functions: expels Ca2+ from cytosol to extracellular environment and recaptures Ca2+ from cytoplasm.
• Role: muscle relaxation, maintaining intracellular Ca2+ concentration.

H+/K+ Pump

• Characteristics: location (parietal gastric cells, kidneys).
• Functions: exchange of H+ for K+ to regulate gastric acid secretion, acid-base balance (e.g., urine).

H+ Pumps

• Location: inner mitochondrial membrane, involved in electron transport and ATP production.
• Role: urine acidification and acid-base balance.

Secondary Active Transport

• Coupled transport utilizing existing ion gradients.
• Direction: Co-transport (same direction) and counter-transport (opposite direction) across the membrane.
• Example: Na+/glucose cotransport, Na+/amino acid cotransporters.

Endocytosis

• Process of bringing material into the cell.
• Forms: phagocytosis, pinocytosis, receptor-mediated endocytosis.
• Characteristics: material engulfing by plasma membrane.

Exocytosis

• Bringing material out of the cell.
• Relationship and balance with endocytosis.

MCQ Questions (Page 54)

• Simple and facilitated diffusion characteristics