Lab #6: Neurophysiology Simulation Background Neurons (Fig 6.1) are cells in the nervous system that are used conduct signals at high speed from one part of the body to another. This enables rapid, precise responses to occur in order to compensate for changes in the environment. Neurons are able to send signals at high speed due to their ability to generate and conduct an electrical signal called an action potential down the length of their axons. An action potential is a brief reversal of the membrane potential, so that for a brief interval at a segment of the axon the intracellular fluid just inside of the plasma membrane is more positive than is the extracellular fluid just outside the plasma membrane. This signal is typically generated at the axon hillock of the neuron, and requires the opening of voltage-gated ion channels — specialized pore-like trans-membrane proteins that open to allow ion passage in response to changes in the relative charge difference across the plasma membrane. There are two different types of voltage-gated ion channels important for the generation action potentials: those specific for sodium ion (Na+), and those specific for potassium ion (K+). In the intervals between action potentials (i.e., when the neuron is “resting”) the two types of ions are kept at different concentrations across the plasma membrane (Fig 6.2). Na+ is maintained at higher concentrations outside the cell than inside the cell. Conversely, K+ tends to be accumulated at higher concentrations inside the cell than outside the cell. The potential for movement of these ions across the cell membrane is thus influenced by the concentration gradients for each ion. Moreover, charge differences across the cell membrane affect the potential for diffusion of these ions. The interior of cells is typically more negatively charged than is the outside of the cell, due to negative charges on certain side-chains of the amino acids of proteins inside the cell, phosphorylated compounds (e.g., ATP), etc. As a result, under resting conditions, there is a strong electrochemical gradient favoring the flow of Na+ into the cell, and a weak electrochemical gradient favoring the flow of K+ out of the cell. Ion concentrations are maintained at relatively constant levels, however, due to the normally low permeability of the plasma membrane to Na+ and low-level activity of the Na+/K+ pump, which pumps Na+ back out into the extracellular fluid and K+ back into the intracellular fluid. The distribution of charged particles across the cell membrane at rest generates the resting potential of the cell membrane, which is variable among different neurons, but typically around -70 mV. The membrane potential (the difference in overall charge across the plasma membrane) of the neuron can change if the relative difference in charges across the membrane is changed. The action potential is generated by just such a redistribution of charged particles across the membrane. By opening large numbers of voltage-gated channels, the permeability of the membrane to Na+ and K+ is increased markedly, allowing the ions to flow along their respective electrochemical gradients from one side of the membrane to the other. Figure 6.2. Distribution of ions across the plasma membrane during resting potential. Different font sizes for Na+ and K+ indicate differences in relative concentration. AxonDendritesSchwann CellsNucleusAxon TerminalsCell BodyAxon Hillock Fig 6.1. Illustration of a neuron and its major associated structuresHowever, in order for voltage-gated ion channels to open and allow this redistribution of ions across the plasma membrane, the membrane potential itself needs to be changed from resting level by a minimum amount (threshold). Changing the membrane potential to the threshold level causes a redistribution of charged areas within the protein itself, causing a shape change in the channel and opening the passage for the ion. The changes in membrane potential needed to induce the voltage-gated ion channels to open are typically due to the binding of chemical signals (e.g., neurotransmitters) in the extracellular environment to chemically-gated ion channels in the dendrites and cell body of the cell, which increase the permeability of the membrane to certain ions. Physical factors such as mechanical distortion of the plasma membrane or extreme temperature changes, as well as other chemical changes that may affect the shape of proteins in the plasma membrane (e.g. pH), can also alter the permeability of the plasma membrane to certain ions. Moreover, changes in the concentration gradients of the ions themselves across the cell membrane can alter the membrane potential, as the movement of the ion across the membrane through fixed open channels may be changed. In some cases, the resultant change in charge distribution depolarizes the membrane (moves the membrane potential closer to 0 mV), and thus moves the membrane potential towards the threshold value. In other cases, the membrane may become hyperpolarized (more negative, further away from 0 mV), which typically moves the membrane potential away from the threshold value needed to open the voltage-gated ion channels. An action potential begins when the plasma membrane at the axon hillock is depolarized to threshold. This induces the opening of the voltage-gated ion channels (Figs 6.3 and 6.4). The channels specific for Na+ open very quickly, thus there is a rapid increase in the permeability of the plasma membrane to Na+. Na+ rapidly flows into the interior of the cell along its electrochemical gradient, and drives the depolarization phase of the action potential. The membrane is fully depolarized to 0 mV, but even then Na+ continues to flow into the interior of the cell, so the fluid inside the cell becomes more positive than the adjacent extracellular fluid, and the membrane polarity is reversed from normal resting levels. The membrane potential rises to ~ +30 mV, but then the flow of Na+ into the cell effectively stops – not because Na+ has reached equilibrium, but because the voltage-gated Na+ channels close at that potential, cutting off the flow of Na+. At approximately the same time the flow of Na+ stops, the voltage-gated K+ channels, which began opening at threshold but require more time to open than do the voltage-gated Na+ channels, begin to open in earnest (Figs. 6.4 and 6.5). Since it is now more positive inside the