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5th & 6th LecturesMon 26 & Wed 28
Jan 2009
Vertebrate PhysiologyECOL 437 (MCB/VetSci 437)Univ. of Arizona, spring 2009
Kevin Bonine & Kevin Oh
1. FinishSolutes + Water
2. Neurons
NeuronsChapter 11
2
Housekeeping, 26 January 2009
Readings
Today: Chapters 4 & 11Wed 28 Jan: Chapter 11LAB Wed 28 Jan: Bisbal & Specker 1991
(see website for links to papers)Fri 30 Jan: Chs 11 & 12Mon 02 Feb: Ch12, Slowinski Article
Lab discussion leaders: 04 Feb1pm – Dan, Michelle3pm – Maria, Jay
Lab discussion leaders: 28 Jan1pm – Steve, Ami3pm – Ty, George
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p. 214, Silverthorn2001. 2nd ed. Human Physiology. Prentice Hall
Nervous SystemNeuronsMembranesIons
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What are neurons for?
How do they work?
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Figure 11.1 Neuronal and hormonal signaling both convey information over long distances
Integration& Control
Nervous vs. Endocrine
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Nervous System
- Neurons / Nerve Cells- Glial Cells (support)
- Signalling via combinationof Electrical and Chemical
- Integrate informationAFFERENT
Comprises
- Coordinate ResponseEFFERENT
5-2 Randall et al. 2002
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“Squid axons are important to physiologists, and to the squid.”Hill et al. 2004, p.281
Sir Alan Hodgkin, Nobel Prize 1963
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Figure 11.7 Recording the resting membrane potential of a squid giant axon
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Neurons:
Hill et al. 2004, Fig 11.1
10Hill et al. 2004, Fig 11.2
1. PNS2. CNS
3. Metabolic support
4. Phagocytes/immune
4 types of Glial Cells
Outnumber neurons 10:1 in mammalian brain
Glial Cells Support Function of NS
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Osmotic Properties of Cells and Relative Ion Concentrations
Na+Na+ K+K+
Cl-Cl-
4-12 Randall et al. 2002
Ca+
Ca+To understand how the NS works we need to return to
Membrane Details
12
Movement Across Membranes
Electrochemical Gradient
Concentration gradient
Electrical gradient
Electrochemical equilibrium
Equilibrium potential (Ex in mV)
Na+Na+
--
--
-
-
-
-
-
-
-
++
+
+
+
+
+
+
++
++
K+K+
--
--
-
-
-
-
-
-
-
++
+
+
+
+
+
+
++
++
when [X] gradient = electrical gradient
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Equilibrium potential (Ex in mV)
“Every ion’s goal in life is to make the membrane potential equal its own equilibrium potential (Ex in mV)”
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1. To change Vm:A Small Number of Ions actually moverelative 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]
Membrane Potential
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Figure 11.11 The membrane potential results from relatively few charges sitting on the membrane
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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)
5. emf determines which direction a given ion (X) will move when the membrane potential is known
4. Equilibrium Potential (Ex in mV):~The equilibrium potentials of all the permeableions (a function of their established gradients) will determine the membrane potential of a cell
emfx = Vm - Ex
- K+ for example
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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, determinemembrane potential
18Hill et al. 2004, Fig 11.4
How do we measure membrane potential?
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Osmotic Properties of Cells and Relative Ion Concentrations
Na+Na+ K+K+
Cl-Cl-
4-12 Randall et al. 2002
Ca+
Ca+How do we calculate the
value of an individual equilibrium potential, or the resting potential of a
cell?
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Figure 11.12 Ion pumps help maintain the concentration of major ions in intracellular and
extracellular fluids
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Equilibrium potential (Ex in mV)
“Every ion’s goal in life is to make the membrane potential equal its own equilibrium potential (Ex in mV)”
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Osmotic Properties of Cells and Relative Ion Concentrations
Na+Na+ K+K+
Cl-Cl-
Permeabilities
K+ >> Na+ ; Cl-
A- (includes proteins, phosphate groups, etc.)
4-12 Randall et al. 2002
Ca+
Ca+
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Randall et al. 2002
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- outside is zero by convention
Membrane Potential (Vm in volts or mV)
K+, Na+- Vrestabout -60 mV
Measurement At Rest
5-7 Randall et al. 2002
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Figure 11.10 Selective permeability of a membrane gives rise to a membrane potential
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Nernst equation: E = lnRTzF
CoutCin
whereE = equilibrium membrane potentialR = gas constantT = absolute temperaturez = valenceF = Faraday’s constant
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Equilibrium Potential
- Calculate for a given type of ion using thesimplified Nernst Equation:
0.058 [X]outEx = log z [X]in
0.058 [Na+]outENa= log z [Na+]in
0.058 120 mMENa= log1 10 mM
= 63 mV (or 0.063 V)
remember Equilibrium potential (Ex in mV)when [X] gradient = electrical gradient
See p. 282 in Hill
2nd edition
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Membrane PotentialTo calculate:
- Nernst for single ion
- Goldman equation for multiple ions
Vm = Ex if only one ion ‘driving’
5-14 Randall et al. 2002
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Nernst Question
Calculate EK if[K+]inside = 140 mM[K+]outside = 2.5 mM
If the resting membrane potential is –60 mV, which way will K+ ‘want’ to move (in or out of the cell)?
Which way will Na+ want to move?
Which way will K+ want to move if membrane potential is -110 mV? 30 mV?
OUT
IN
IN
-101 mV
OUT
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Osmotic Properties of Cells and Relative Ion Concentrations
Na+Na+ K+K+
Cl-Cl-
4-12 Randall et al. 2002
Ca+
Ca+ Goldman Equation?
Donnan Equilibrium?-eg. Cl- is a permeating anionVs.non-permeating anions
A- (includes proteins, phosphate groups, etc.)
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Figure 11.13 The Goldman equation and the “voltage thermometer”
Importance of PERMEABILITY
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channels
membrane bilayer
Hill et al. 2004, Fig 11.5c
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conductance = reciprocal of resistance
Membrane Potentials and Electricity
vs.capacitance
5-10 Randall et al. 2002deltaV = IRChange in Voltage = current x resistance
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Hill et al. 2004, Fig 11.5a,b
Current from + to –(follow cations)
Tau = time constant(2 - 20 ms)(time to reach 63% max)
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Hill et al. 2004, Fig 11.6a,b
36Hill et al. 2004, Fig 11.6c
Lambda = length constant(distance at which 37% voltage change)
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channels
membrane bilayer
Hill et al. 2004, Fig 11.5c
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)
http://en.wikipedia.org/wiki/Cable_theory
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Action Potentials
5-2 Randall et al. 2002
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Nervous System
- Presynaptic- Postsynaptic
2 Interneuronsentirely in CNS
Synapse
- Presynaptic- Postsynaptic
3 Motor Neurons effector organsincl. muscle, gland
1 Sensory Neuronsreceive stimuli
graded
all-or-
none
5-2 Randall et al. 2002
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Action Potential
- Changes in ion permeability…- Changes in membrane potential
-Voltage-gated ion channelsvs. ligand-gated
All-or-None fromspike-initiating zone
- Na+, K+, (Ca2+)
graded
all-or-
none
5-2 Randall et al. 2002
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41Silverthorn 2001. 2nd ed. Human Physiology. Prentice Hall
Frequency and number!
How does a given neuron convey urgency?
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-Moves information; high-speed communication
Action Potentials
-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 (Vm)
- Na+ and K+ responsible for AP character…
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-Threshold
-Many channelsfor Na+
-Then manychannels for K+
+60 vs. -100
emf
-Voltage gated
5-20 Randall et al. 2002
current
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Fig 11.24 Cardiac muscle fiber action potential
?
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Membrane Potential
-Hyperpolarization1 and 2
Terms:
-Depolarization3 and 4
-Repolarization3 and 4
-Threshold Potentialsee 4 (50% time get AP)
5-9 Randall et al. 2002
46Hill et al. 2004, Fig. 11.11
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Randall et al. 2002
48
Silverthorn 2001. 2nd ed. Human Physiology. Prentice Hall
25
49
Hill et al. 2004, Fig. 11.12
Action Potential
Changes in Permeabilitiesas Channels Open/Close
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local current flow causes Vm change
Voltage-gated Na+ channels
AP is regenerative
6-4 Randall et al. 2002
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Figure 11.16 The Hodgkin cycle produces the rising phase of the action potential
Hodgkin Cycle (~Feed Forward)
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Figure 11.20 The molecular structure of voltage-gated Na+ channels
How does depolarization open these?
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-Refractory Periods
-Absolute
-Relative
OPENINACTIVECLOSED
CLOSED
Voltage-gatedNa+ channels
~ Toilet Analogy…
5-17 Randall et al. 2002
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closedopen inactive closed
Current- bottom
Voltage -top 5-22 Randall et al. 2002
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Figure 11.17 Patch-clamp recording of single-channel currents
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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…
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57
Silverthorn 2001. 2nd ed. Human Physiology. Prentice Hall
58
Hill et al. 2004, Fig. 11.11
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Figure 11.23
What are each of these red traces representing?
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Figure 11.23
What are each of these red traces representing?
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61Silverthorn 2001. 2nd ed. Human Physiology. Prentice Hall
graded
62
Silverthorn 2001. 2nd ed. Human Physiology. Prentice Hall
32
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-Role of local current flow
(no APs past here)
-But can see local graded potential diminishing
p.161 Randall et al. 2002
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-Receptor potential isgraded and decremental
-Magnitude of graded receptor potentialdetermines frequency of APs (~all of the same size)
-Alternate between graded psps and all-or-none APs
psp = postsynaptic potential
-Neurotransmitter Release
6-1 Randall et al. 2002
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65
Silverthorn 2001. 2nd ed. Human Physiology. Prentice Hall
66
EPSP and IPSP
Excitatory or Inhibitory Postsynaptic Potentials
Na+
Ca2+
K+
Cl-
EPSP IPSP
psc
psc
psp
Graded currentcausing graded
potential:
6-19 Randall et al. 2002
34
67Hill et al. 2004, Fig 12.5
Integration
SUMMATION-Temporal-Spatial (and Temporal)
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Silverthorn 2001. 2nd ed. Human Physiology. Prentice Hall
How can you have IPSP where Ex greater (more +) than Vrest?
35
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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 (Erev; = Ex) for a given ion whose permeability across the membrane has just increased.
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Reversal PotentialOpening channel for a given ion species X means Vm will move toward Ex
Erev is the reversal potential
Use Nernst to calculate for one ion speciesGoldman equation for multiple ions
Can’t change membrane potential beyond Erev for a given ion(s) and its channels
ACh opens for K+ and Na+, so Erev between EK and ENa
EPSP and IPSP
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Synaptic Efficacy
Presynapticinhibition
e.g., Cl-, K+
or alter Ca2+
IPSP
NT release via exocytosis: the role of Ca2+
6-22 Randall et al. 2002
72Silverthorn 2001. 2nd ed. Human Physiology. Prentice Hall
37
73Hill et al. 2004 pg. 330
Presynapticinhibition
Substance P – facilitates pain sensation
Enkephalin – endorphin (opiod) that minimizes pain sensation
74
-How increase AP conduction velocity?
1 –Diameter
2 -Insulation
-Long axons requireinsulation (support cells)
-glial cells for myelination(fatty tissue) aka:
-Schwann cells in peripheral nerves-Oligodendrocytes in CNS
6-6 Randall et al. 2002
38
75
Silverthorn 2001. 2nd ed. Human Physiology. Prentice Hall
GLIAL:-Schwann cells in
peripheral nerves-Oligodendrocytes in CNS
76
Nodes of Ranvier & Saltatory Conduction
6-7 Randall et al. 2002
39
77Silverthorn 2001. 2nd ed. Human Physiology. Prentice Hall
longitudinal currentvs. cross membrane
78
Multiple sclerosis caused by demyelination
Randall et al. 2002
40
79
A given nerve bundle can have multiple axons, each with different conductionvelocities.
6-8 Randall et al. 2002
