Molecular and Cellular Bases of Physiology L02 - Summer 24 PDF

Molecular and Cellular Bases 2. Cell transport Andre Azevedo, DVM, MSc Visiting Professor of Veterinary Physiology [email protected] Learning objectives for this lecture Differentiate passive and active transport across the membrane List the different types of passive transport and...

Molecular and Cellular Bases 2. Cell transport Andre Azevedo, DVM, MSc Visiting Professor of Veterinary Physiology [email protected] Learning objectives for this lecture Differentiate passive and active transport across the membrane List the different types of passive transport and describe how they work Understand osmosis List the different types of active transport and describe how they work Describe endocytosis and exocytosis Cell transport video https://www.youtube.com/watch?v=I1MZG6508IM Cell transport The transport of substances through cell membrane The majority of biochemicals do not pass readily through a phospholipid bilayer Semi-permeable barrier Lipid soluble substances can penetrate Water-soluble substances usually can’t Water molecules CAN! – too small rate depends on the cell type Cell transport The membrane proteins are important for the transport Their molecular structure interrupts the lipid bilayer, providing an alternative pathway Can act as: CHANNELS - a space all the way through the protein molecule allows transport to the other side CARRIERS/TRANSPORT PROTEINS - bind to molecules or ions, and conformational changes in the protein move the substances to the other side of the membrane Channels and Carriers are usually selective for some types of molecules or ions Cell transport Can occur via one of two basic processes: PASSIVE TRANSPORT or DIFFUSION Molecules move down its concentration gradient Does not require the cell to expend energy - uses kinetic energy ACTIVE TRANSPORT Molecules move against the gradient It uses cellular energy to move molecules Passive transport (diffusion) SIMPLE DIFFUSION Through the lipid bilayer I.e., osmosis (diffusion of water) FACILITATED DIFFUSION Through carriers or transporters Passive transport (diffusion) SIMPLE DIFFUSION No specific protein is needed (some authors disagree) The rate of diffusion is directly proportional to the lipid solubility of the substance I.e.: Oxygen, nitrogen, carbon dioxide, and alcohols can diffuse directly Permeability of different molecules Small hydrophobic molecules readily dissolve in lipid bylayers Small uncharged hydrophylic molecules also diffuse across the bilayer, but more slowly Lipid bilayers are almost impermeable to ions, no matter how small they are (charged and high degree of hydration) Osmosis The net movement of water caused by a concentration difference of water across a membrane Water can diffuse through the lipid bilayer and through selective protein channels called aquaporins Aquaporins are highly specialized, and there are at least 13 types in various cell types of mammals Pressure can also influence water diffusion The amount of pressure required to stop osmosis is called OSMOTIC PRESSURE Osmosis Passive transport (diffusion) FACILITATED DIFFUSION Specific proteins facilitate diffusion across the membrane No cellular energy is required Carrier/Channel only acts upon specific substrates The rate of transport will reach a maximum based on the number of carriers available in the membrane - cannot rise greater than the Vmax of the carrier protein Different from simple diffusion, where the rate of the diffusion is proportional to the concentration of the diffusing substance Facilitated diffusion proteins A. CARRIER PROTEINS Responsible for facilitated diffusion of sugars, amino acids, and nucleosides Bind to specific molecules, undergo conformational changes and allow the molecule to pass Facilitated diffusion proteins B. CHANNELS Open pores in the membrane allowing ions and small hydrophilic molecules to pass Many protein channels are highly selective Allow passage of only one, or just a few different specific ions or molecules (not a universal passage) Selectivity comes from characteristics like: Diameter Shape Nature of the electrical charges and bonds along its inside surface Important channels in the cell membrane AQUAPORINS Water channels through which water molecules can cross the membrane much more rapidly than they can diffuse through the phospholipid bilayer Increase speed of diffusion Important channels in the cell membrane ION CHANNELS Mediate the passage of ions across the plasma membrane The gate of the channel controls ion permeability Some are always open (leak channels) while others have gates Several kinds of stimuli can open ion gated-channels Changes in voltage across the membrane Ligand (intra or extracellular) Mechanical stimulus (like stretching/pressure – but yet poorly understood) Important channels in the cell membrane ION CHANNELS – VOLTAGE-GATED CHANNELS Present in the plasma membrane of all excitable cells Nerve, muscle, endocrine, and egg cells Responsible for neuron’s ability to transmit information along its length and to release neurotransmitters There is a range of membrane potentials that cause them to open CHANNEL’S THRESHOLD = minimum membrane potential that causes the opening of the channel Important channels in the cell membrane ION CHANNELS – LIGAND-GATED CHANNELS Found in the membrane of: skeletal muscle cells some neurons of the autonomic nervous system and brain Channel open in response to ligand binding I.e.: Acetylcholine released from neuron binds to Nicotinic Acetylcholine Receptor in the skeletal muscle cells Neuromuscular junction video https://www.youtube.com/watch?v=eTYe1CtjJRE Active transport PRIMARY ACTIVE TRANSPORT The energy is derived directly from the breakdown of ATP or similar The transport is against a concentration/electrochemical gradient SECONDARY ACTIVE TRANSPORT Energy is provided by the concentration gradient of the driving ion Transporter protein couples the movement of an ion (typically Na+ or H+) down its electrochemical gradient to the uphill movement of another molecule or ion against a concentration/electrochemical gradient CO-TRANSPORT COUNTER-TRANSPORT Primary active transport Secondary active transport CO-TRANSPORT or SYMPORT The simultaneous transport of two substances across a membrane in the same direction The protein can be called a Symporter I.e., Na+-D-Glucose co-transporter (SGLT-1) Secondary active transport COUNTER-TRANSPORT or ANTIPORT The simultaneous transport of two substances across a membrane in opposite directions The protein can be called an Antiporter I.e., Na+ H+ antiporter in the kidney Transcellular or epithelial transport In some places of the body, substances must be transported across the cell from one ECF compartment to another Basic mechanism: Active transport through the cell membrane on one side Either simple diffusion or facilitated diffusion through the membrane on the opposite side Transcellular or epithelial transport passive transport (facilitated diffusion) active transport ⭣ [K+] ⭣ [K+] [K+] [Na+] ⭣ [na+] [Na+] Endocytosis / Exocytosis Impermeable molecules can be transported across the membrane by means other than membrane proteins Using part of the membrane itself as a carrier Endocytosis PHAGOCYTOSIS Ingestion of large particles PINOCYTOSIS Ingestion of small particles RECEPTOR MEDIATED ENDOCYTOSIS I.e., Cholesterol Exocytosis CONSTITUTIVE SECRETION All cells No signal sequence Proteins are incorporated into the plasma membrane, and extracellular matrix or are signaling proteins REGULATED SECRETION Specialized cells Need signal to stimulate fusion and release to the cell exterior Endocytosis / Exocytosis video https://www.youtube.com/watch?v=nXrU6AaPp88 Questions?