Lectures 4 - Columbia University

3/20/2017
Organismic Biology
Bio 207
Lecture4
Internal communication: neurons, resting membrane potentials,
action potentials; voltage-gated channels
Dr. Simchon
Remember
Next week is your 1st exam
Will cover lectures 1-3 and Tutorial 1
The labs are not covered
Exam: multiple choice, multiple answers, calculations,
graphs, essay
1
3/20/2017
Remember salt balance
Hyper-osmoregulator
Hypo-osmoregulator
Hyper-osmoregulator
Hypo-osmoregulator
2
3/20/2017
Osmotic Hyper-regulation
100 mOsm
Passive diffusion of
Solutes
Passive diffusion of
Solutes
ECF (organism)
300 mOsm
Active uptake of
ECF (organism)
900 mOsm
Active uptake of
Solutes
Solutes
Which organism will spend more energy?
Mode of osmo-regulation
Hyper-osmoregulator C and B
ECF conc
(mOsm)
C
D
B
B
A
A = line of identity
Hypo-osmoregulator D and B
Environment conc (mOsm)
Which organism will spend more energy at external 100mOsm?
Which organism will spend more energy at external 900mOsm?
3
3/20/2017
Role of ADH and ANP
ANP = Atrial Natriuretic (sodium = Na) hormone = Diuretic hormone
ADH = Antidiuretic hormone
Renal Regulation
The ability to concentrate urine by reabsorption of filtered water, will save
us from having to drink large amount of water and to have frequent trips to
the bathroom .
The ability to concentrate urine depends on:
(a) countercurrent system.
(b) Antidiuretic Hormone (ADH) level
(c) ANP level and sodium reabsorption
4
3/20/2017
Medium term adaptation to lower its water output
Important for exam
 Increase ADH  concentrate urine (increase reabsorption of water)
How can you tell that urine is concentrated?
 By measuring urine/plasma osmolarity ratio
Urine Osm/Plasma Osm = 1
Expected ADH level
Urine Osm/Plasma Osm = 0.5
Expected ADH level
Pl. Osm = 300; U Osm = 300 mOsm
Pl. Osm = 300; U Osm = 150 mOsm
Urine Osm/Plasma Osm = 4
Expected ADH level
Pl. Osm = 300; U Osm = 1200
What is the long term adaptation to concentrate urine?
Figure 26.7 The interpretive significance of the osmotic
U/P ratio
5
3/20/2017
Figure 15.14 The
action of an
antidiuretic hormone
6
3/20/2017
The Effects of ADH
7
3/20/2017
New stuff 2nd exam
Nervous system Agenda
• Intro to communication
– Nervous system overview
– Resting Membrane Potential
– Action Potentials
– Action Potential Conduction
– The Synapse
– Post-synaptic cell responses
Coordination of organismic function:
the thread
• Integrating the function of tens of trillions of cells
organized into hundreds of tissues and many organ
systems: the evolution of multicellular organisms has
depended upon the ability of cells to communicate
with each other across great distances
• responding rapidly and in a sustained way over long
periods of time
• control systems are necessary
8
3/20/2017
Two types of coordination pathways
• Neuronal:
rapid signaling
specifically addressable (individual cells and
locations)
example: fine movement control; sensory input
• Hormonal:
mid- to long-term signaling
widely broadcast with all receptive cells responding
examples: cellular metabolism; organ function
Two types of system-level communication
9
3/20/2017
The Nervous System
Chapter 48
Topics to be covered
1. Organization of the Nervous System
2. How does information carried out and transported in nerve?
3. How does information submitted from one nerve to another?
Organization of the Nervous System
• Central nervous system (CNS)
– Brain and spinal cord
– Integration and command center
• Peripheral nervous system (PNS)
– Carries messages to and from the spinal cord and brain. That portion
of the nervous system that is outside the brain and spinal cord.
10
3/20/2017
Organization of the Nervous System
Organization of the Nervous System
Central Nervous System
Peripheral Nervous System
afferent
efferent
11
3/20/2017
Organization of the Nervous System
Central Nervous System (CNS)
Enteric Nervous System
Peripheral Nervous System (PNS)
Efferent division of PNS
Sensory division of
PNS
Sensory receptors
Efferent division of PNS
Autonomic involuntary
Sympathetic
Somatic voluntary
Parasympathetic
Heart, lung, etc
Skeletal muscles
Afferent Pathway = Input to brain
Sensory - 5 senses:
o Sight
o Smell
o Taste
o Touch
o Hearing
12
3/20/2017
How does information carried out and transported in nerve?
Electrical impulses = Action Potential
Very fast
How does neural information travel?
13
3/20/2017
What is the signal nerves use?
How can cells act like wires?
• electrical impulses traveling along the nerve cell from
end to end: dendrites to axon terminus
• Neurotransmission: chemical transmission links nerve
cells and the cells with which they communicate
Dendrites
Cell body
Presynaptic
terminal
Source: Animal Physiology, 3rd Edition by Hill, Wyse and Anderson, Sinauer Press
What electrical properties of cells permit
information transfer in nerves?
• all cells have electric properties and polarity
• Most cells are passive and do not conduct
charge
• neuronal cells are active and do conduct a
charge down their length
• to understand both active and passive cell
potentials we must understand the cell
membrane
14
3/20/2017
Electricity Basics
• Electric current (I): net movement of charge –
measured in amperes or milliamperes – A or mA
(ions in cells; electrons in wires)
• Voltage: separation of charge/ electrical potential
difference (V) – measured in volts or millivolts - V
or mV
• Resistance (R): element that impedes current
flow – measured in Ohms - Ω
• Capacitance (C): storage of charge – measured in
farads - F
Ohms Law
∆V
I = ----R
I = current
V = voltage difference
R = resistance
15
3/20/2017
All cells have an electric potential difference
from inside to outside: Membrane potential
•difference in charge between the inside and outside of the cell membrane
•usually negative inside relative to outside
•polarity is determined by the distribution of ions across the cell membrane
Transmembrane charge
16
3/20/2017
Membrane Potential (Vm)
• Membrane potential (Vm) is the transmembrane
potential: the electrical charge difference across the
membrane that results from the separation of charges
across the cell membrane. It has a value and a sign.
• Sign refers to the intracellular charge. Example: if Vm
= -70 mV indicates that the inside of cell is 70 mV
more negative than the outside of cell.
• Determinants: Permeability to specific ions (R) and
ionic concentrations (Cin – Cout)
What do we find if we measure
cellular and extracellular ion
concentrations?
17
3/20/2017
Some typical extracellular and intracellular fluid values
Extracell
(mEq/L)
Intracellular
(mEq/L)
2
74
Sodium - Na+
145
15
Potassium - K+
5
150
Calcium - Ca++
1
0.0001
Magnesium - Mg++
3
26
Chloride - Cl-
108
10
Bicarbonate - HCO3-
27
10
PO4-
2
113
non-electrolyte
10
10
Protein
Why are there concentration differences
inside to outside?
• Active transport of some ions - Na+-K+-ATPase
• Varying passive diffusion of others based on individual permeability
18
3/20/2017
Electrogenic pumps
• Do not pump equal charge in and out
• Na+-K+=ATPase pumps Na+-K+ in a 3:2 ration, thus
producing a net current, and is electrogenic
• This functions to offset passive leaking of ions
across the membrane, and to directly impact Vm
• What would be the Na+-K+ pumping ratio of an
electroneutral pump?
Only a few ions are needed to create polarity
• 110,000 anions and 110,000
cations on each side of
membrane
• Only 6 pairs of ions create a 90mV membrane potential
19
3/20/2017
Passive Transport of Particles
A. Particles without charge
B. Particles with charge
Simple diffusion of particles without charge
Compartment 1
Compartment 2
A
A
C1
>
C2
Concentrations C1 > C2
2
1
Substance A will move from
to _______
The Driving force is: Concentration gradient
Diffusion Fick law = K (C1 - C2)
20
3/20/2017
Simple diffusion of particles without charge
Compartment 1
Compartment 2
A
C1 >
Concentrations C1 > C2
Substance A will move from
The Driving force is:
A
C2
to _______
Electrical effects in simple diffusion
• Positive charges are attracted to negative charges
• Similar charges repel each other
• A large electrical difference may cause a solute to move in such
a direction so as to increase the concentration difference.
21
3/20/2017
Electrical effects in simple diffusion
Compartment 1
-
+ Compartment 2
A+
A+
C1
=
Concentrations C1 = C2
Substance A will move from
The Driving force is:
C2
(same)
to _______
Electrical effects in simple diffusion
Compartment 1
-
+ Compartment 2
A+
A+
C1
>
C2
Concentrations C1 > C2
Substance A will move from
The Driving force is:
to _______
Fick diffusion equation
22
3/20/2017
Nernst Equilibrum
Movement will stop when : ____________________________
Nernst Equilibrium: Vm = Ei
Vm = electrical potential of membrane
Ei = chemical potential of membrane
[Nernst = f(C1-C2)]
Electrochemical gradient
Ions and semi-permeable membranes
Equilibrium both sides
Concentrations of solutes equal and ion charge
balanced
If an ion is too large to cross the membrane, other
electrical charges will move to maintain a balance in
charge and conc.
23
3/20/2017
Ions and semi-permeable membranes
Equilibrium both sides
Concentrations of solutes equal and ion
charge balanced
If an ion is too large to cross the
membrane, other electrical charges
will move to maintain a balance in
charge and conc.
Electrical effects in simple diffusion
Outside cell
Inside cell
Na+
K+
24
3/20/2017
If only K+ is permeable
Outside cell
Inside cell
K+
If only Na+ is permeable
Outside cell
Inside cell
Na+
25
3/20/2017
THE NERNST EQUATION
Since both the concentration gradient and the transmembrane potential affect the
movement of ions, we must be able determine the relative magnitudes of these two forces.
The Nernst equation does this. Using the equation, a Nernst potential can be calculated
for every ion in the cell. What does that tell you? If you force the cell to be at the Nernst
potential for a certain ion, then that ion will not cross the membrane, even if a channel for
it is open, because the electrical potential will exactly balance the concentration
difference.
RT
C1
Em = ---------ln-------zF
C2
-1
-1
R = universal gas constant (8.314 J mol K ), T = absolute temperature (in K), z
=valence of ion (i.e. Cl- = -1), F = Faraday's constant (96485 C).
Resting membrane potentials depend
upon selective permeability to ions
and active ion pumping
26
3/20/2017
Balancing concentration and charge
• Both the concentration gradient (Cin - Cout) and the
transmembrane potential (Vm) affect the movement of ions so
we must be able determine the relative magnitudes of these
two forces
• The Nernst equation does this. Using the equation, a Nernst
potential can be calculated for every ion in the cell.
• What does that tell you? If you force the cell to be at the
Nernst potential for a certain ion, then that ion will not cross
the membrane, even if a channel for it is open, because the
electrical potential will exactly balance the concentration
difference.
Nernst equation
Membrane potential due to the distribution of one ion if
it were fully permeable
RT Cout
E = ----- ln ----zF
Cin
E is membrane potential (electromotive force)
R is the gas constant (8.314 J mol-1 K-1),
T is absolute temperature (in K)
z is the valence of the ion (i.e. Cl- = -1),
F is Faraday’s constant – charge per mole of ions (96,485 C).
C is the ionic concentration inside and outside
27
3/20/2017
Simplified Nernst equation
(at 37o C)
61
Cout
E = ---- log10 ----z
Cin
E is membrane potential in mV
C is the ionic concentration inside and out
z is the valence of the ion
Ei is the equilibrium potential for a
particular ion
• The value of the membrane potential at which the
ion is at electrochemical equilibrium and there is
no net ionic movement across the membrane
• Meaning: the electrical force on the ion is exactly
balanced by the chemical concentration (force)
• This condition does not exist for any ion in the
body except for transiently
28
3/20/2017
Nernst Equilibrium
At Nernst equilibrium: Vm = Ei
•
•
Vm = electrical potential difference across membrane
Ei = chemical potential across membrane for a given ion
[Nernst = f(C1-C2)]
At 37oC
At 25oC
Em = 61/z log10 Cout/Cin
Em = 58/z log10 Cout/Cin
C1 - C2 is the concentration gradient (assuming it is across the
plasma membrane – distance is a parameter for a gradient)
Complete the Table
Ion
Concentration
Inside Cell outside cell
K+
Na+
Cl-
150 mEq/L
15 mEq/L
10 mEq/L
At 37ºC: 60 log10 Cout/Cin
Nernst Equilibrium
Magnitude
4 mEq/L
145 mEq/L
108 mEq/L
At 37 º C:
1. What will be the electrical charge across membrane if only K+ is permeable? What is the
polarity?
2. What will be the electrical charge across membrane if only Na+ is permeable? What is the
polarity?
3. What will be the electrical charge across membrane if only Cl- is permeable? What is the
polarity
29
3/20/2017
But more than one ion is responsible for Vm
• Vm is largely determined by K+ concentrations inside
and outside because the cell membrane is most
permeable to K+
• However, other ions, particularly Na+ and Cl-, are also
important for Vm
• Other ions can be ignored because of either very low
membrane permeabilities (ie. HCO3- ) or very low
concentrations (H+)
• The Goldman equation combines the contributions of
K+, Na+ and Cl- to derive Vm
Goldman Equation (GHK)
RT
Pk [K+]o + PNa [Na+]o + PCl [Cl-]i
Vm = ---- log ----------------------------------------F
Pk [K+]i + PNa [Na+]i + PCl [Cl-]o
Pk , PNa and PCl are the relative permeabilities for K+ , Na+ and Cl-
30
3/20/2017
Actual Vm may be anywhere between these:
If the membrane were
permeable only to Na+ :
ENa = 58 log (145/15) = +59 mV
Membrane potential (mV)
+59
Pk [K+]o + PNa [Na+]o
Vm = 58 log ---------------------------Pk [K+]i + PNa [Na+]i
If the membrane were
permeable only to K+ :
Ek = 58 log (4/150) = -94 mV
ENa
0
-65
Em (resting)
-94
EK
Extreme cases
For the squid giant axon:
• 25o C
• Ignoring Cl• [K+]o = 20 mM [K+]i = 400 mM
• [Na+]o = 440 mM [Na+]I = 44 mM
[K+]o : [K+]I = 0.05
[Na+]o : [Na+]I = 10
31
3/20/2017
Actual Vm may be anywhere between these:
If Pk = 10 X Pna :
10 [20] + 1 [440]
Vm = 58 log ----------------------10 [400] + 1 [44]
= 58 log (640/4044)
= -46.4 mV
Membrane potential (mV)
+58.0 ENa
0
-46.4
-75.0
Vm
EK
Complete
mV
+60
-------ENa
0
-70
-90
--------Vm
---------EK
time
32
3/20/2017
Phases of Action Potential in nerve and skeleton muscle
Concentration gradients exist across the plasma
membrane. Specifically, there are ________.
A. more sodium ions inside and more potassium
ions outside the plasma membrane.
B. more potassium ions inside and more sodium
ions outside the plasma membrane.
C. more sodium and potassium ions inside the
plasma membrane than outside.
D. equal concentrations of sodium and potassium
ions outside the plasma membrane.
33
3/20/2017
The value of the typical nerve resting
membrane potential is ________.
A.
B.
C.
D.
–70 mV
+30 mV
–90 mV
–55 mV
The plasma membrane is more
permeable to ________.
A. sodium ions
B. potassium ions
34
3/20/2017
The resting membrane potential
depends on each item below, EXCEPT:
A. the concentration gradient for sodium ions.
B. the greater permeability of the plasma
membrane to potassium ions.
C. the greater permeability of the membrane
to anions rather than cations.
D. the greater number of potassium leak
channels.
The Na+/K+ pump transports ________.
A. Na+ into and K+ out of the cell
B. Na+ out of and K+ into the cell
C. equal numbers of Na+ out of and K+ into
the cell
D. more K+ into than Na+ out of the cell
35
3/20/2017
∆V
This equation (Ohm’s law) states that: I = ----R
A.The greater the voltage gradient, the higher is the current
B.The greater the resistance, the higher is the voltage
gradient
C.The lower the current the larger is the resistance.
D.The greater the voltage gradient, the lower is the
resistance.
For the 1st exam
1. Benchmarks Unit 1: Fluids and osmoregulation
2. Kidney calculate GFR, countercurrent, Hormonal regulation (ADH, Aldosterone)
3. Graphing, short essays
4. Tutorial 1: Solutes, solutions and osmolality. Aquatic environments
36
3/20/2017
Key Differences in Definition results from an environmental
change
Acclimation:
occurs within an individual organism and changes within a lifetime
change is reversible due to experimental conditions or can be in
laboratory or controlled setting
Acclimatization:
occurs within an individual organism and changes within a lifetime
change is reversible
due to natural conditions
Adaptation:
occurs within a group of individuals (population)
changes over several generations
change is not reversible
due to either natural or experimental conditions (artificial selection)
genetic change and evolutionary response
37