5 th & 6 th Lectures Mon 26 & Wed 28 Jan 2009 Vertebrate Physiology ECOL 437 (MCB/VetSci 437) Univ. of Arizona, spring 2009 Neurons Chapter 11 Kevin Bonine & Kevin Oh 1. Finish Solutes + Water 2. Neurons 1 Housekeeping, 26 January 2009 Readings Today: Chapters 4 & 11 Wed 28 Jan: Chapter 11 LAB Wed 28 Jan: Bisbal & Specker 1991 (see website for links to papers) Fri 30 Jan: Chs 11 & 12 Mon 02 Feb: Ch12, Slowinski Article Lab discussion leaders: 04 Feb 1pm Dan, Michelle 3pm Maria, Jay Lab discussion leaders: 28 Jan 1pm Steve, Ami 3pm Ty, George 2 1
p. 214, Silverthorn 2001. 2 nd ed. Human Physiology. Prentice Hall Nervous System Neurons Membranes Ions 3 What are neurons for? How do they work? 4 2
Figure 11.1 Neuronal and hormonal signaling both convey information over long distances Nervous vs. Endocrine Integration & Control 5 Nervous System Comprises -Neurons/ Nerve Cells - Glial Cells (support) - Signalling via combination of Electrical and Chemical - Integrate information AFFERENT - Coordinate Response EFFERENT 5-2 Randall et al. 2002 6 3
Squid axons are important to physiologists, and to the squid. Hill et al. 2004, p.281 Sir Alan Hodgkin, Nobel Prize 1963 7 Figure 11.7 Recording the resting membrane potential of a squid giant axon 8 4
Neurons: Hill et al. 2004, Fig 11.1 9 4 types of Glial Cells Outnumber neurons 10:1 in mammalian brain 3. Metabolic support 4. Phagocytes/ immune 2. CNS 1. PNS Glial Cells Support Function of NS Hill et al. 2004, Fig 11.2 10 5
Osmotic Properties of Cells and Relative Ion Concentrations K+ Na+ K+ Na+ Ca+ Ca+ 4-12 Randall et al. 2002 Cl- Cl- To understand how the NS works we need to return to Membrane Details 11 Movement Across Membranes Electrochemical Gradient Electrical gradient Concentration gradient K+ + + - + - + - + - + - + - - + - + - + - + - K+ + Electrochemical equilibrium Equilibrium potential (E x in mv) when [X] gradient = electrical gradient Na+ + + - + - + - + - + - + - - Na+ + - + - - + + - + 12 6
Equilibrium potential (E x in mv) Every ion s goal in life is to make the membrane potential equal its own equilibrium potential (E x in mv) 13 Membrane Potential 1. To change Vm: A Small Number of Ions actually move relative to the number present both inside and outside the cell 2. Concentration gradients (previously established by ATPase pumps) are not abolished when the channels for an ion species open [Gradients allow for work to be done, e.g., action potential sends signal along axon] 14 7
Figure 11.11 The membrane potential results from relatively few charges sitting on the membrane 15 Membrane Potential 3. Driven by ions that are permeable to the membrane (and have different [ ] in as compared to [ ] out a.k.a. gradient created with ATP) -K+ for example 4. Equilibrium Potential (E x in mv): ~The equilibrium potentials of all the permeable ions (a function of their established gradients) will determine the membrane potential of a cell 5. emf determines which direction a given ion (X) will move when the membrane potential is known emf x = V m - E x 16 8
Membrane Potential 6. Resting Membrane Potential driven by K+ efflux and, to a lesser extent, Na+ influx 7. Na+/K+ ATPase pump generates gradients that, for these permeable ions, determine membrane potential 17 How do we measure membrane potential? Hill et al. 2004, Fig 11.4 18 9
Osmotic Properties of Cells and Relative Ion Concentrations K+ Ca+ Ca+ 4-12 Randall et al. 2002 Na+ K+ Na+ Cl- Cl- How do we calculate the value of an individual equilibrium potential, or the resting potential of a cell? 19 Figure 11.12 Ion pumps help maintain the concentration of major ions in intracellular and extracellular fluids 20 10
Equilibrium potential (E x in mv) Every ion s goal in life is to make the membrane potential equal its own equilibrium potential (E x in mv) 21 Osmotic Properties of Cells and Relative Ion Concentrations K+ Ca+ Ca+ Na+ K+ Na+ Cl- Cl- 4-12 Randall et al. 2002 Permeabilities K+ >> Na+ ; Cl - A - (includes proteins, phosphate groups, etc.) 22 11
Randall et al. 2002 23 Measurement At Rest Membrane Potential (V m in volts or mv) -outside is zero by convention -V K +, Na + rest about -60 mv 5-7 Randall et al. 2002 24 12
Figure 11.10 Selective permeability of a membrane gives rise to a membrane potential 25 Nernst equation: E = RT ln zf C out C in where E = equilibrium membrane potential R = gas constant T = absolute temperature z = valence F = Faraday s constant 26 13
Equilibrium Potential - Calculate for a given type of ion using the simplified Nernst Equation: E x = 0.058 log [X] out z [X] in See p. 282 in Hill 2 nd edition E Na = 0.058 log [Na + ] out z [Na + ] in E Na = 0.058 log 120 mm 1 10 mm = 63 mv (or 0.063 V) remember Equilibrium potential (E x in mv) when [X] gradient = electrical gradient 27 Membrane Potential To calculate: - Nernst for single ion V m = E x if only one ion driving -Goldman equation for multiple ions 5-14 Randall et al. 2002 28 14
Nernst Question Calculate E K if [K + ] inside = 140 mm [K + ] outside = 2.5 mm -101 mv If the resting membrane potential is 60 mv, which way will K+ want to move (in or out of the cell)? OUT Which way will Na+ want to move? IN Which way will K+ want to move if membrane potential is -110 mv? 30 mv? IN OUT 29 Osmotic Properties of Cells and Relative Ion Concentrations K+ Ca+ Ca+ 4-12 Randall et al. 2002 Na+ K+ Na+ Cl- Cl- Goldman Equation? Donnan Equilibrium? -eg. Cl - is a permeating anion Vs. non-permeating anions A - (includes proteins, phosphate groups, etc.) 30 15
Figure 11.13 The Goldman equation and the voltage thermometer Importance of PERMEABILITY 31 channels membrane bilayer Hill et al. 2004, Fig 11.5c 32 16
Membrane Potentials and Electricity conductance = reciprocal of resistance vs. capacitance deltav = IR Change in Voltage = current x resistance 5-10 Randall et al. 2002 33 Current from + to (follow cations) Hill et al. 2004, Fig 11.5a,b Tau = time constant (2-20 ms) (time to reach 63% max) 34 17
Hill et al. 2004, Fig 11.6a,b 35 Lambda = length constant (distance at which 37% voltage change) 36 Hill et al. 2004, Fig 11.6c 18
channels membrane bilayer Want to learn more about tau and lambda? Check out CABLE THEORY (you will even see some familiar names pop up in the history of this scientific idea) Hill et al. 2004, Fig 11.5c http://en.wikipedia.org/wiki/cable_theory 37 Action Potentials 5-2 Randall et al. 2002 38 19
Nervous System Synapse -Presynaptic - Postsynaptic 1 Sensory Neurons receive stimuli 2 Interneurons entirely in CNS 3 Motor Neurons effector organs incl. muscle, gland graded all-or-none -Presynaptic - Postsynaptic 5-2 Randall et al. 2002 39 Action Potential All-or-None from spike-initiating zone - Changes in ion permeability - Changes in membrane potential -Voltage-gated ion channels vs. ligand-gated graded all-or-none -Na +, K +, (Ca 2+ ) 5-2 Randall et al. 2002 40 20
Frequency and number! How does a given neuron convey urgency? Silverthorn 2001. 2 nd ed. Human Physiology. Prentice Hall 41 Action Potentials -Moves information; high-speed communication -Thoughts, Sensations, Memories, Movements etc. -Moves SIGNAL without decrement -AP possible because: 1 Ionic gradients across membrane 2 Creates electrochemical gradient and therefore source of potential energy 3 When ion channels open, ions move down their electrochemical gradients and rapidly change the membrane potential (V m ) - Na+ and K+ responsible for AP character 42 21
-Threshold 5-20 Randall et al. 2002 -Voltage gated -Many channels for Na+ -Then many channels for K+ +60 vs. -100 emf current 43 Fig 11.24 Cardiac muscle fiber action potential? 44 22
Membrane Potential Terms: -Hyperpolarization 1 and 2 -Depolarization 3 and 4 -Threshold Potential see 4 (50% time get AP) -Repolarization 3 and 4 5-9 Randall et al. 2002 45 Hill et al. 2004, Fig. 11.11 46 23
Randall et al. 2002 47 Silverthorn 2001. 2 nd ed. Human Physiology. Prentice Hall 48 24
Action Potential Changes in Permeabilities as Channels Open/Close Hill et al. 2004, Fig. 11.12 49 Voltage-gated Na+ channels local current flow causes Vm change AP is regenerative 6-4 Randall et al. 2002 50 25
Figure 11.16 The Hodgkin cycle produces the rising phase of the action potential Hodgkin Cycle (~Feed Forward) 51 Figure 11.20 The molecular structure of voltagegated Na + channels How does depolarization open these? 52 26
-Refractory Periods CLOSED OPEN INACTIVE CLOSED Voltage-gated Na+ channels -Absolute -Relative ~ Toilet Analogy 5-17 Randall et al. 53 2002 closed open inactive closed Voltage -top 5-22 Randall et al. 2002 Current- bottom 54 27
Figure 11.17 Patch-clamp recording of single-channel currents 55 How would you make the membrane in the axon hillock/spike initiation zone more, or less, likely to send an AP? In less than a second In three months Across evolutionary time 56 28
Silverthorn 2001. 2 nd ed. Human Physiology. Prentice Hall 57 Hill et al. 2004, Fig. 11.11 58 29
Figure 11.23 What are each of these red traces representing? 59 Figure 11.23 What are each of these red traces representing? 60 30
graded Silverthorn 2001. 2 nd ed. Human Physiology. Prentice Hall 61 Silverthorn 2001. 2 nd ed. Human Physiology. Prentice Hall 62 31
-Role of local current flow (no APs past here) -But can see local graded potential diminishing p.161 Randall et al. 2002 63 -Receptor potential is graded and decremental -Magnitude of graded receptor potential determines frequency of APs (~all of the same size) -Neurotransmitter Release -Alternate between graded psps and all-ornone APs psp = postsynaptic potential 6-1 Randall et al. 2002 64 32
Silverthorn 2001. 2 nd ed. Human Physiology. Prentice Hall 65 EPSP and IPSP Excitatory or Inhibitory Postsynaptic Potentials EPSP IPSP psp psc Na + K + Ca 2+ Cl - Graded current causing graded potential: psc 66 6-19 Randall et al. 2002 33
Integration SUMMATION -Temporal -Spatial (and Temporal) Hill et al. 2004, Fig 12.5 67 How can you have IPSP where Ex greater (more +) than Vrest? Silverthorn 2001. 2 nd ed. Human Physiology. Prentice Hall 68 34
In conjunction with 2 or 3 students around you, explain how a change in the postsynaptic membrane potential from -70 to -65 could actually be inhibitory. (Assume that -70 is resting and that -50 is threshold for an AP.) e.g., reversal potential (E rev ; = E x ) for a given ion whose permeability across the membrane has just increased. 69 Reversal Potential Opening channel for a given ion species X means Vm will move toward Ex Erev is the reversal potential Can t change membrane potential beyond Erev for a given ion(s) and its channels Use Nernst to calculate for one ion species Goldman equation for multiple ions ACh opens for K+ and Na+, so Erev between E K and E Na EPSP and IPSP 70 35
Presynaptic inhibition IPSP 6-22 Randall et al. 2002 Synaptic Efficacy e.g., Cl -, K + or alter Ca 2+ NT release via exocytosis: the role of Ca 2+ 71 Silverthorn 2001. 2 nd ed. Human Physiology. Prentice Hall 72 36
Presynaptic inhibition Substance P facilitates pain sensation Enkephalin endorphin (opiod) that minimizes pain sensation Hill et al. 2004 pg. 73330 -How increase AP conduction velocity? 1 Diameter 2 -Insulation -Long axons require insulation (support cells) -glial cells for myelination (fatty tissue) aka: -Schwann cells in peripheral nerves -Oligodendrocytes in CNS 6-6 Randall et al. 2002 74 37
GLIAL: -Schwann cells in peripheral nerves -Oligodendrocytes in CNS Silverthorn 2001. 2 nd ed. Human Physiology. Prentice Hall 75 Nodes of Ranvier & Saltatory Conduction 6-7 Randall et al. 2002 76 38
longitudinal current vs. cross membrane Silverthorn 2001. 2 nd ed. Human Physiology. Prentice Hall 77 Randall et al. 2002 Multiple sclerosis caused by demyelination 78 39
A given nerve bundle can have multiple axons, each with different conduction velocities. 6-8 Randall et al. 2002 79 40