Module 5 PDF - Biology Past Paper

Module 5 Ion Channels Hydrophilic pores for inorganic ions moving down the electrochemical gradient; ion channels do not bind ions but provide a preferred path. Compared to aqueous pores, (1) they show ion selectivity (e.g., diameter), (2) they open/close (regulated by phosphorylation). Ion...

Module 5 Ion Channels Hydrophilic pores for inorganic ions moving down the electrochemical gradient; ion channels do not bind ions but provide a preferred path. Compared to aqueous pores, (1) they show ion selectivity (e.g., diameter), (2) they open/close (regulated by phosphorylation). Ion channels are “gated”: voltage-gated, mechanically-gated, ligand-gated channels. Common channels are the K+ leak channels, permeable to K+ and open even in an unstimulated cell. Glossary Membrane potential: voltage difference across a membrane due to different numbers of positive/negative ions. Non-excitable cells have a constant membrane potential; resting membrane potential refers only to excitable cells (e.g., nerve, muscle), in an unstimulated state ~ -70 mV. Electrochemical gradient: the combined concentration gradient and membrane potential; driving force for ion movement across the membrane. Equilibrium potential: the membrane potential, at which the net flow of a specific ion through any open channels is 0 (influx = efflux); the chemical and electrical forces for this ion are in balance. Osmotic Balance Osmotic balance is maintained by the sodium/potassium (Na+/K+) pump. Solutes that cannot pass freely through the membrane contribute to osmotic pressure: examples are the impermeable organic anions inside cells. The plasma membrane is "effectively impermeable” to Na+ due to the Na+/K+ pump (K+ ions are redistributed by a great number of leak channels). Membrane Potential and the K+ Gradient The main contributors to the resting membrane potential: (1) passive ion movements (i.e., leak channels), and (2) Na+-K+ pump moving Na+ out and K+ in. Major players: Na+, K+, Cl-, and organic anions. K+ has a dominant effect on the resting potential because the membrane is more permeable to K+ (there are more K+ leak channels than Na+ leak channels). K+ ions move through K+ leak channels to almost achieve their equilibrium. How Is the Membrane Potential Established Assume that initially, there is no voltage gradient across the plasma membrane, and [K+] is higher inside the cell. Driven by the concentration gradient, K+ leaves the cell through K+ leak channels. As K+ moves out, it leaves behind negative charges, creating a membrane potential that opposes further K+ efflux. The net flow of K+ becomes zero when the electrical field balances the K+ concentration gradient. The equilibrium of no net flow of ions across the membrane defines the resting membrane potential. The Nernst equation expresses the equilibrium condition and allows the calculation of the theoretical resting membrane potential. Module 5 The Nerve Cell Function Neuron: the axon conducts signals away, and the dendrites receive signals from axons of other neurons. Signal: change in the electrical potential across the plasma membrane, and spread of this electrical disturbance in one part of the cell to other parts. Action potential: an electrical stimulus beyond a certain threshold that triggers electrical activity along the plasma membrane and is sustained by amplification. Action potentials are facilitated by voltage-gated cation channels. Voltage-gated Cation Channels The initial depolarization of the membrane is by ligand-gated sodium channels. The depolarization beyond a threshold opens voltage-gated Na+ channels to start the action potential. The influx of Na+ depolarizes the membrane further and opens more Na+ channels (self-amplification). The potential changes from -70 mV to ~ +50 mV, almost reaching the Na+ equilibrium potential. When the net electrochemical force for Na+ is ~ zero: (1) the Na+ channels are inactivated, (2) voltage-gated K+ channels open, and K+ ions exit; the increasing [K+] outside results in hyperpolarization. Inactivation gates close the Na channels almost as soon as their activation gates are open. Therefore, the depolarization is transitory and moves in one direction along the membrane only! The K channels also have inactivation gates. They close around the equilibrium potential of potassium Action Potential and Refractory Period Action potential: transient self-propagating electrical excitation in the membrane. Hyperpolarization: voltage-gated K+ channels open to repolarize the membrane, and K+ moves out of the cell, bringing the membrane potential closer to the K+ equilibrium potential. Recovery/refractory potential: when the cell is unable to conduct an impulse; there is the absolute and relative refractory period. Absolute refractory phase: when a second action potential cannot be initiated. Relative refractory phase: after the absolute refractory period, initiation of a second action potential is inhibited, but not impossible Other absolute refractory phase is due to the inactivation gates of the Na channels being closed! Myelination and Action Potential Propagation Myelination: the plasma membrane of glial cells wrapped around the axon (myelin sheath). Glial cells: Schwann cells myelinate axons in peripheral nerves, oligodendrocytes (etc.) do so in the central nervous system. Myelination increases the rate of an action potential. The myelin sheath is interrupted by nodes of Ranvier, where almost all the Na+ channels in the axon are concentrated. Depolarization of the membrane at one node almost immediately spreads passively to the next node; thus, an action potential propagates along a myelinated axon by jumping from node to node (saltatory conduction). Module 5 Ca2+ Initiates Muscle Contraction The action potential of a muscle cell is supported by voltage-gated Na+ channels and causes depolarization of the T-tubules; the T-tubules are deep invaginations of the plasma membrane (sarcolemma) of the muscle cells. The spread of an action potential via the T-tubules opens dihydropyridine receptors, and these open Ca2+-release channels (i.e., ryanodine receptors) in the sarcoplasmic reticulum (SR) → cytosolic [Ca2+] increases. The increase in cytosolic [Ca2+] is transient, as cytosolic Ca2+ is pumped back into SR by Ca2+-ATPase, against its concentration gradient. Release of Ca2+ Mediated by Ryanodine Receptors (RYRs) In skeletal muscle, voltage-gated dihydropyridine receptors in the sarcolemma contact ryanodine receptors in the membrane of the sarcoplasmic reticulum. In response to a change in voltage, the dihydropyridine receptors undergo a conformational change, leading to a conformational change in the ryanodine receptors. The ryanodine receptors open, and Ca2+ ions exit from the ER lumen into the cytosol. Other mechanisms of opening the Ryr by DHPR have been proposed as well. Transmitter (Ligand)-gated Ion Channels Convert chemical into electrical signals; open in response to ligands and change membrane permeability to ions. ~Insensitive to membrane potential, do not produce a self-amplifying excitation (an action potential is triggered only if the local membrane potential increases to open voltage-gated channels). Neurotransmitters are sent from cell to cell at synapses; the presynaptic and postsynaptic cells are separated by a synaptic cleft. The change in potential of the presynaptic cell releases neurotransmitters; these ligands diffuse in the synaptic cleft to bind ligand-gated ion channels on the postsynaptic cell; neurotransmitters are removed by enzymes or taken up by surrounding cells. Chemical Synapses Are Excitatory or Inhibitory Excitatory neurotransmitters open Na+ channels (inward flow) to depolarize the postsynaptic membrane. Inhibitory neurotransmitters open Cl- channels (inward flow) or K+ channels (outward flow), making it harder to depolarize the postsynaptic membrane. Acetylcholine, glutamate, and serotonin are usually excitatory and GABA and glycine are inhibitory. Module 5 Neuromuscular Transmission the action potential reaches the nerve terminal → depolarizes the plasma membrane → opens voltage- gated Ca channels extracellular Ca²⁺ enters the terminal → releases acetylcholine (ACh) vesicles into the synaptic cleft → ACh activates ligand-gated cation channels on the sarcolemma the depolarization of the sarcolemma opens voltage-gated Na⁺ channels to start an action potential that spreads the action potential activates voltage-gated DHPR in the T-tubules leading to Ca²⁺ release from the sarcoplasmic reticulum into the cytosol (see slide 13); as a result, the myofibrils contract (reviewed in a future lecture) Putting It Together Ion channels form pores to allow inorganic ions to cross the membrane down their electrochemical gradients. Channels are “gated,” and respond to a change in membrane potential (voltage-gated channels) or binding of a neurotransmitter (transmitter/ligand-gated channels). K+ leak channels have a role in determining the resting membrane potential across the plasma membrane. Voltage-gated cation channels generate self-amplifying action potentials in electrically excitable cells. Transmitter-gated ion channels convert chemical signals to electrical signals at chemical synapses. Excitatory neurotransmitters open transmitter-gated cation channels and thereby depolarize the postsynaptic membrane to fire an action potential.