Membrane Transport

• diffusion is a passive process of solutes moving from high to low concentrations
• non polar, uncharged molecules can pass through the membrane through passive diffusion
• rate of diffusion affected by: surface area, concentration gradient, thickness of cell membrane, weight of molecule
• molecules that undergo passive diffusion: O2, CO2, steroid hormones, lipid soluble drugs
• steroid hormones include testosterone, oestrogen, cortisol
• Na+ is always higher conc outside of the cell
• facilitated/simple diffusion requires a channel or carrier to mediate diffusion, it's for large/charged molecules
• leaky channels are important within neurons, e.g. the K+ leaky channel moves K+ from high concentration in the cell to low concentration outside the cell which controls resting membrane potential
• voltage gated channel; responds to change in voltage, has to hit a specific voltage threshold to open and allow ions to rush into the cell, important for action potentials in the neurons
• ligand-gated channel; e.g. Acetyl Choline in neuromuscular junction: when Ach binds the gate opens and allows Na+ to rush in, leading to an action potential and muscle contractions
• mechanically gated channel; pressure opens the channel and allows inflow of ions, e.g. Na+ which increases action potential or pain receptors which stimulate sensory nerves to stimulate pain signal
• channel mediated facilitated diffusion; present when there is a specific stimulus or open all the time. e.g. Glucose, higher conc outside the cell, channels (GLUT) will have to move glucose down its conc gradient
• GLUT4 is found in adipose and muscle tissue
• insulin regulates glucose, and stimulates the expression of GLUT4 to bring in lots of glucose into the cell
• primary active transport uses ATP as primary energy source to move substances from low to high concentration
• ATPase on channels, breaks down ATP into ADP and Pi + energy used to drive movement of ions against conc gradient
• Na+/K+ ATPase: moves 3Na+ out of cell (down gradient) and 2K+ into cell (against gradient)
• Increased insulin -> increased activity of Na+/K+ ATPase, increases metabolism activity
• Increased Na+/K+ ATPase activity: more ATP utilisation, increased heat
• Digoxin is used to inhibit Na+/K+ ATPase, lower [Na+] outside of the cell, can't move into the cell, Ca2+ can't move out of the cell (antiporter mechanism) which causes Ca2+ build up in muscle cell, increase contractility of muscle cells, more blood pumped out of heart
• ATP needed to pump Ca2+ from sarcoplasm to sarcoplasmic reticulum for storage, if Ca2+ stays in sarcoplasm it would continue contraction.
• increased sympathetic activity: increased norepinephrine and epinephrine -> increased PKA expression which stimulates Ca2+ ATPase channels to allow more Ca2+ into sarcoplasmic reticulum which means more Ca2+ out -> increased contraction
• Proton pump inhibitors (PPIs) are used to treat gastric and duodenal ulcers, for people that produce too much HCl
• secondary transport moves molecules against their concentration gradient, using the energy energy stored by another molecule going down its cncentration gradient, indirect use of ATP
• the more hydrophillic a solute is, the higher the activation energy, the energy is used to strip water from polar molecules
• in simple diffusion removal of shell is endergonic and activation energy is high
• transporter proteins reduce activation energy by forming non covalent interactions with the dehydrated solute to replace hydrogen bonding and provides a hydrophilic transmembrane pathway
• channels are gated holes in the membrane, once open they allow ions to pass through, flow through a channel stops when the gate is closed or the electrochemical gradient is no longer there to act as a driving force
• what gates channels?

  ligand binding

  voltage sensing channels

  cell turgor

  pH
• channels are fast and selective with minimal conformational change associated with movement across membrane, substrates can only go down gradient, it's not energetically favourable to go against
• osmotic gradient is balanced by an opposite osmotic gradient due to high conc of inorganic ions in extracellular fluid
• in the kidney antidiuretic hormone (vasopressin) regulates concentrations of aquaporins in plasma membrane
• aquaporins have to allow passage of water molecules while blocking ions. the channels have a narrow pore that allows water to pass through in a single file following the path of carbonyl oxygens that line one side of the pore
• aquaporin impermeable to H3+; the channels have 2 Asn which bidn the oxygen of central water, imposing bipolarity on single-file column. the central water molecule can't participate in H+ relay
• aquaporins functional characteristics: bidirectional, fast, transports not only water but sometimes glycerol
• aquaporin structural characteristics: forms tetramer (each protomer is a channel with its own pore), 6THM, 2 half helices, NPA motif in the middle, Cys182 at the top which plugs the pore, amphipathic pore and hydrogen bonding interaction of water
• bigger polar compounds are excluded from aquaporins, anything bigger than water won't get through = selectivity filter. Proton exclusion, maintains pH and proton gradient
• Some roles of aquaporins: seed germination, cytoplasm homeostasis, petal and leaf movement, maintenance of cell turgor under various stresses, and fruit ripening.
• Low, but significant sequence similarity between members – signature sequence
• What is meant by semipermeable membrane?

  Allows some substances (uncharged, small) to pass through while blocking others (charged, polar and large).