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Physiology 3140A
Donglin Bai

Take-Home Messages For Dr. Bai’s Section On 3140A Midterm Introduction • Electrical current in the body is carried by positive and negative ions, rather than electrons Lecture 1: Ion Channels • All excitable cells are able to fire action potentials because of membrane-bound ion channels. • Pores in ion channels are selective and dynamically-regulated by sensor movement • Gating of ion channels can be achieved through voltage (change in potential), ligand- binding or mechanical means (change in conformation). • Most ion channels organize by transmembrane domains with alpha-helical structure. • Hydration depends on charge and size (or charge density – amount of charge per unit volume). • More water means greater hydration number, causing the ion to have decreased mobility. • Carbonyl oxygen atoms interact with K ions by providing the perfect amount of energy for removing the hydration shell and stabilizing the ions passing through. • Negatively-charged residues attract cations to the pore opening, while anions are repelled. Lecture 2: Molecular Structure Of Ion Channels • nAChRs are heteromeric, pentameric ion channels at NMJ that are selective for cations passage (due to the TM2 domain) upon binding of one acetylcholine to each of the 2 alpha subunits. + • K “charged paddle” channels are tetrameric voltage-gated ion channels (with 6 domains per subunit) that allow passage of K ions via the selectivity of the H5 pore loop and the S4 voltage sensor. • Ca and Na channels are voltage-gated channels comprised of 1 protein and 4 super- + domains (each resembles subunit of K channel subunit) that work via movement of activation/inactivation gates. + • A-Type K channel possesses N-terminus (ball-and-chain model) responsible for inactivation (not present in delayed rectifier K channel). + • Triethlyammonium (TEA) binds to H5 pore loop blocking K ion passage, while Tetradotoxin (TTX) blocks opening of Na voltage-gated channel. • 1 gap junction is comprised of 2 connexons (hemichannels), which are formed by 6 connexins (subunits) each. • Gap junctions are involved in bidirectional communication through signaling molecules 2+ and nutrients and can be inactivated by increased intracellular acidity and Ca . Lecture 3: Methods Of Measurement • Sharp electrodes (current clamp) measure membrane potential (emulating in vivo conditions), but can’t record any single channels and have increasingly high resistance. • The voltage command of the voltage clamp can work to hyperpolarize as well as depolarize the cell from resting membrane potential, but the voltage command is always obeyed by the cell. • Voltage clamp measures current or conductance at fixed voltage, but is technically demanding. • Above point of reference refers to outward (positive) current, while below point of reference refers to inward (negative) current. • The number of channels and the channel’s conductance (ability to pass ions) are the two factors determining the amplitude of the current response. • Patch recordings are able to measure single channel activities and have low resistance, but result in the destruction of the native state of the cell. • The amplitude of a single-channel current is always the same at a constant membrane potential. • Each channel used in a single channel current response opens randomly and with variable duration. Lecture 4: Ionic Distribution & Nernst Equation • Concentration gradients are maintained because the membrane is not permeable to all ions equally, electrical gradients help maintain concentration gradients, and ionic pumps exist (long term). • While the chemical force depends on the concentration gradient and the absolute temperature (T), electrical force depends on the charge and electrical gradient (potential). • The total force (sum of the chemical and electrical forces) will determine the direction of ion movement. • A diffusion potential (voltage gradient across membrane) arises due to certain ions + moving faster across the cell membrane (e.g. K vs. acetate). • In the long-term, an electrochemical equilibrium (a dynamic process) or char
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