SI Wednesday October 14, 2009 Membrane Physiology Glossary of Terms and Useful Info Efflux: Flow of ions out of the cell Influx: Flow of ions into the cell Resting EM: Resting Membrane Potential: -70mV Eion: Ionic Equilibrium Potential for a given ion. AKA the value of the membrane potential if cell is only permeable to the given ion. Based on: 1)Concentration Gradient IN vs OUT of given ion 2)Electrical Gradient EK: Ionic Equilibrium Potential for K+: approx -90mV ENa: approx +66mV ECl: approx -42mV Voltage/Potential: Measure of the charge difference across a membrane (IN with respect to OUT) Permeability: Extent to which certain ions can flow across a membrane → Dictated by how many channels are open for that ion Depolarization: Membrane potential becomes closer to zero (less negative) Hyperpolarization: Membrane potential becomes farther from zero “[ ]”: the symbol/abbreviation for concentration. Example: Under typical conditions [K+] IN >>>>> [K+] OUT Review Exercises: Identify a couple of physiological examples where establishing concentration gradients does some sort of work in the body. What is the “work” that can be accomplished by the electrochemical gradients built into the neuron at rest and why is this essential for the nervous system? 1) Secondary Active Transport: A sodium concentration gradient pointing into the cell ([Na+] OUT > [Na+] IN) can be utilized to transport substances such as glucose or amino acids into the cell 2) (FYI!) Proton gradients across the mitochondrial inner membrane: Chemical bonds in energy metabolites such as glucose contain electrons in high-energy states (high potential energy). As these electrons flow through the electron transport proteins, they move from a high energy to a low energy state. This energy is used to build an H+ concentration gradient that is high in the intermembrane space and low in the matrix. As hydrogen ions flow back down their concentration gradient and into the matrix, they turn a “water-wheel” protein called ATP synthase, giving it energy to synthesize ATP from ADP and P (lots of potential energy in the phosphate bonds). Since ATP drives all other cellular processes, this is the most fundamental example of concentration gradients doing work in the body. 3) Electrochemical Gradients built across the neuronal membrane at rest allow the nervous system to communicate RAPIDLY across long distances. This is essential to the nervous system which must make real time adjustments to its outputs (motor) in response to its input (sensory). Recall the three important properties of ion channels. What are the four major categories of ion channels? Identify which “potential” each is associated with. (see Resting Membrane Potential Worksheet Solutions) What are the three most important transmembrane proteins in maintaining the resting membrane potential? (see Resting Membrane Potential Worksheet Solutions) What would happen to the Resting Membrane Potential if the extracellular concentration of potassium ions suddenly became abnormally low. 1) EK would become more negative: since there is a stronger concentration gradient driving K+ , more efflux would be observed before the concentration gradient is balanced by the electrical gradient which would necessarily be more negative. Try it out in the bonus activity 1 SI Wednesday October 14, 2009 Membrane Physiology Short Answer Exercises: Describe the four basic characteristics of graded potentials. In what anatomical regions of the neuron are graded potentials typically generated? Typically generated in the soma and dendrites, which are rich in chemically gated ion channels that can be activated by synapses with other neurons. (from slide #99 and table 12-2 in the text) 1) “The transmembrane potential is most affected at the site of stimulation and decreases with distance” 2) “The effect spreads passively due to local currents” 3) “The graded change can be hyperpolarization or depolarization. The nature of the change depends on the properties of the membrane channel involved.” 4) “The stronger the stimulus, the greater is the change in the transmembrane potential and the larger is the area affected” We all have our thresholds. What does it mean for a neuron to have a threshold? Threshold is a physical property built into the voltage gated channels. When the membrane potential is more negative than the threshold, the channel stays closed. When the membrane potential becomes increasingly positive it approaches the threshold value…above threshold the channel will open for a certain amount of time. Because voltage gated channels are not present until the initial segment of the axon, all excitatory stimuli spread passively within the dendrites and soma(there are no channels to propagate the stimuli) and therefore must be sufficiently strong to depolarize the initial segment above the threshold value if an action potential is to be initiated. Label the following on the image below SEE THE ACTION POTENTIAL / SYNAPTIC TRANSMISSION WORKSHEET FOR THE FULLY LABELLED DIAGRAM Graded EPSPs Threshold Value VGNaC Activation Gate Opens VGNaC Activation Gate Closes VGNaC Inactivation Gate Closes VGNaC Inactivation Gate Opens VGKC Opens VGKC Closes Absolute Refractory Period Begins (and why) Absolute Refractory Period Ends (and why) Relative Refractory Period Begins Relative Refractory Period Ends Rising Phase / Depolarization Falling Phase / Repolarization Undershoot and Overshoot At the top of the rising phase (when voltage gated K + channels open) in what direction do the electrical and chemical gradients point respectively for K+ ? (see Action Potential / Synaptic Transmission Worksheet Solutions) If an action potential was engaged in a debate with a graded potential, what would it assert as the fundamental differences between the two parties? (SEE TABLE 12-4 IN THE TEXTBOOK) If you experimentally depolarized a resting axon beyond threshold half-way along the axon, an action potential would propagate bidirectionally….both towards the soma (backpropagation) and towards the synaptic terminal(s). Under actual physiological conditions, when an action potential is initiated at the initial segment of the axon, there is no backpropagation observed despite the fact that influx of sodium ions at that same point in the axon would theoretically depolarize all adjacent regions of the membrane. Why? (Be brief but specific). (see Action Potential / Synaptic Transmission Worksheet Solutions) What is the difference between continuous vs. saltatory conduction? (see Action Potential / Synaptic Transmission Worksheet Solutions) What is the evolutionary significance of myelination? (see Action Potential / Synaptic Transmission Worksheet Solutions) 2 SI Wednesday October 14, 2009 Membrane Physiology Bonus Fun Activity: Go to www.nernstgoldman.physiology.arizona.edu Click ‘launch now’. Set to ‘Goldman Equation’ at the upper right corner. Manipulate the permeability as well as the intracellular and extracellular concentrations of the various ions to observe the effect on the membrane potential and the equilibrium potential for that ion. You can restore the default settings at the bottom right hand corner. SUPER FUN!! Multiple Choice Fun: 1. The activation of ligand-gated ion channels is always associated with: A. Generation of action-potentials B. Change in the permeability to an ion C. Depolarization D. Hyperpolarization 2. If you were an axon establishing a new connection with another neuron, where would you want to establish that synapse to have to most profound impact on the frequency with which that neuron fires action potentials? A. Dentritic Branches B. Dentritic Spines C. The Axon Hillock D. The point at which dendrites branch from the soma 3. The absolute refractory period is due to: A. Inactivation of voltage-gated sodium channels B. Prolonged opening of voltage-gated potassium channels C. Prolonged opening of potassium leakage channels D. Inactivation of sodium leak channels 4. During an action potential, activity at which type of channel is responsible for the rapid restoration of the resting membrane potential after depolarization has occurred? A. Potassium leak channels B. Voltage-gated sodium channels C. The Na+/K+ ATPase D. Voltage-gated potassium channels 3