a, b, c, d all move solutes by diffusion down concentration gradient
Jan 02, 2016
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a, b, c, d all move solutes by diffusion down concentration gradient
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Final mechanism can work against gradient
e. Active transport
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Final mechanism can work against gradient
e. Active transport
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Final mechanism can work against gradient
e. Active transport
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Final mechanism can work against gradient
e. Active transport
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Pump Protein
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Final mechanism can work against gradient
e. Active transport
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Final mechanism can work against gradient
e. Active transport
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ATP
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Final mechanism can work against gradient
e. Active transport
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ATP
ADP + Pi
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Final mechanism can work against gradient
e. Active transport
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Final mechanism can work against gradient
e. Active transport
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Concentrates against gradient
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Ion pumps
Uniporter (one solute one way):
I- pump in thyroid
Coupled transporters (two solutes)
Symporter (same direction):
Antiporter (opposite directions)
Na+/K+ ATPase in mitochondria
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3. Cells can control solute distribution across their membranes by controlling:
a. Synthesis of integral proteins
b. Activity of integral proteins
c. E supply for pumps
Therefore, expect that solutes would be unequally distributed across membranes
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4. Actual ion distributions
Squid Axon (mM):
ION [CYTOPLASM] [ECF]
Na+ 50 460
K+ 400 10
Cl- 40 540
Ca++ <1 10
A- 350 <1
Organic anions with multiple - charges
COO- on proteins, sulfates, phosphates, etc....
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5. Reasons for unequal distribution
a. Metabolic production of organic anions
A- produced by biosynthetic machinery inside the cell
b. Membrane permeability
impermeable to A-
moderate Cl- permeability
30-50X more permeable to K+ than Na+
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Given a and b, system passively comes to unequal ion distribution
Diffusion of ions governed not only by their concentration gradients, but also their electrical gradients
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Permeable uncharged solutes will come to equilibrium across membranes if no other forces acting
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1 M sucrose
Permeable uncharged solutes will come to equilibrium across membranes if no other forces acting
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1 M sucrose
Permeable uncharged solutes will come to equilibrium across membranes if no other forces acting
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1 M sucrose 0.5 M sucrose
0.5 M sucrose
Permeable uncharged solutes will come to equilibrium across membranes if no other forces acting
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Permeable charged solutes will not come to concentration equilibrium across
membrane if other charged impermeable solutes are present
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Na+
A-
Impermeable
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Na+
A-
K+ Cl-
Permeable
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Na+
A-
K+ Cl-
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Na+
A-
K+ Cl-
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Na+
A-K+
Cl-Na+
A-
K+ Cl-
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Na+
A-K+
Cl-Na+
A-
K+ Cl-
At equilibrium: chemical force driving K+ out
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Na+
A-K+
Cl-Na+
A-
K+ Cl-
At equilibrium: chemical force driving K+ out
is exactly balanced by the electrical force (electromotive force) holding K+ in
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Na+
A-K+
Cl-Na+
A-
K+ Cl-
At equilibrium: chemical force driving K+ out
is exactly balanced by the electrical force (electromotive force) holding K+ in
Result: an unequal ion distribution which will be maintained passively
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Na+
A-K+
Cl-Na+
A-
K+ Cl-
At equilibrium: chemical force driving K+ out
is exactly balanced by the electrical force (electromotive force) holding K+ in
Result: an unequal ion distribution which will be maintained passively
“Donnan Equilibrium”
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Donnan Equilibrium resembles situation in real cell, with one exception:
cell is not maintained passively
Poison real cell and unequal distribution eventually goes away
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c. Cells work via pumps to maintain unequal ion distribution
Na+ “leaks” in down chemical and electrical gradients
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Na+
A-
c. Cells work via pumps to maintain unequal ion distribution
Na+ “leaks” in down chemical and electrical gradients
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Na+
A-
c. Cells work via pumps to maintain unequal ion distribution
Na+ “leaks” in down chemical and electrical gradients
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Na+
A-Na+Na+/K+ ATPase
c. Cells work via pumps to maintain unequal ion distribution
Na+ “leaks” in down chemical and electrical gradients
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Na+
A-
Na+
c. Cells work via pumps to maintain unequal ion distribution
Na+ “leaks” in down chemical and electrical gradients
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Na+
A-
Na+K+
c. Cells work via pumps to maintain unequal ion distribution
Na+ “leaks” in down chemical and electrical gradients
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Na+
A-
Na+
K+
c. Cells work via pumps to maintain unequal ion distribution
Na+ “leaks” in down chemical and electrical gradients
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If Na+ allowed to build up, inside becomes + , drives K+ out, and lose unequal distribution
Na+
A-
Na+
K+
c. Cells work via pumps to maintain unequal ion distribution
Na+ “leaks” in down chemical and electrical gradients
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Therefore, cells use combination of active and passive mechanisms to maintain unequal ion distributions
REASON?
B. Membrane Potentials
1. Significance of unequal distributions
Whenever an ion is unequally distributed across a membrane, it endows the membrane with an electrical potential
“membrane potential” (EM or VM)
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2. Membrane potential measurement
a. Voltmeter
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2. Membrane potential measurement
a. Voltmeter
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2. Membrane potential measurement
a. Voltmeter
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2. Membrane potential measurement
a. Voltmeter
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Inside is -80 mV
2. Membrane potential measurement
a. Voltmeter
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b. Calculate with Nernst equation
EM = RT x ln[ion]outside
FZ ln[ion]inside
R = gas constant, T = abs. temperature
F = Faraday constant, Z = valance
Magnitude of the voltage due to 1 unequally distributed ion is directly proportional to the magnitude of its unequal distribution
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BUT: can't use it for a real cell
only valid for 1 ion
only valid for freely permeable ions
Can use it to calculate voltage due to any one freely permeable ion in a mixture
e.g. K+ = -91 mV
Na+ = +65 mV
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c. Alternative: GOLDMAN EQUATION
accounts for multiple ions
accounts for permeability of each
multiplies [ion] ratios X permeability constant for each ion, then sums
up all to get total membrane EM
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d. CONCLUSION:
In ion mixture, each ion contributes to the overall EM in proportion to its permeability
Most permeable ions contribute the most charge
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Which ion is most permeable?
K+
real cell: inside is -80 mV = resting EM
cell is “negatively polarized”
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EM is due almost exclusively to the unequal distribution of K+
Changes in [K+] alter EM easily
Changes in [Na+] do not alter EM
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All cells have resting potential due to ion distributions
Some cells can use this electrical potential to transmit information
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C. Nervous System Components
1. Glial cells: supportive
diverse functions
support
insulation
protection
communication
up to 90% of nervous system by weight
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2. Neurons
soma: nucleus, usual organelles
dendrites: receptive, input
axon: transmission (microm to m)
axon terminals: synapse, output
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3. Integrated Function of Neurons
Generate and conduct electrical signals for communication or coordination
a. Propagation of electrical signals along individual cells (wires)
b. Communication of electrical information between cells
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c. Model system for study:
Squid giant axon (J.Z. Young)
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c. Model system for study:
Squid giant axon (J.Z. Young)
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D. Electrical Characteristics of Neurons
1. Intracelluar Recording:Hodgkin and Huxley
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D. Electrical Characteristics of Neurons
1. Intracelluar Recording:Hodgkin and Huxley
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D. Electrical Characteristics of Neurons
1. Intracelluar Recording:Hodgkin and Huxley
recording electrode
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D. Electrical Characteristics of Neurons
1. Intracelluar Recording:Hodgkin and Huxley
recording electrode
coupled with stimulating electrode
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D. Electrical Characteristics of Neurons
1. Intracelluar Recording:Hodgkin and Huxley
recording electrode
coupled with stimulating electrode
64Can change EM by adding charge
D. Electrical Characteristics of Neurons
1. Intracelluar Recording:Hodgkin and Huxley
recording electrode
coupled with stimulating electrode
65Can change EM by adding charge
+++
D. Electrical Characteristics of Neurons
1. Intracelluar Recording:Hodgkin and Huxley
recording electrode
coupled with stimulating electrode
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STIMULUS
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STIMULUSmV
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STIMULUS
RESPONSE OF CELL
mV
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STIMULUS
RESPONSE OF CELL
EM
(mV)
mV
0
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STIMULUS
RESPONSE OF CELL
EM
(mV)
mV
0
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EM
(mV)
mV
-80
0
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EM
(mV)
mV
-80
Add negative charge,
EM gets more negative0
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EM
(mV)
mV
-80
HYPERPOLARIZATION
Add negative charge,
EM gets more negative0
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EM
(mV)
mV
-80EM moves away from 0 HYPERPOLARIZATION
Add negative charge,
EM gets more negative0
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EM
(mV)
mV
-80
0
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EM
(mV)
mV
-80
0
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EM
(mV)
mV
-80
Add positive charge,
EM gets more positive0
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EM
(mV)
mV
-80
Add positive charge,
EM gets more positive
DEPOLARIZATION
0
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EM
(mV)
mV
-80
Add positive charge,
EM gets more positive
DEPOLARIZATION
EM moves towards 0
0
80
EM
(mV)
mV
-80
0
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EM
(mV)
mV
-80
0
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EM
(mV)
mV
-80
0
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EM
(mV)
mV
-80
0
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2. Passive responses
a. Magnitude directly proportional to amount of current
Increase current: increase magnitude of passive depolarization
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b. Magnitude inversely proportional to distance from stimulus
Die out locally
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b. Magnitude inversely proportional to distance from stimulus
Die out locally
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b. Magnitude inversely proportional to distance from stimulus
Die out locally
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b. Magnitude inversely proportional to distance from stimulus
Die out locally
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b. Magnitude inversely proportional to distance from stimulus
Die out locally
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b. Magnitude inversely proportional to distance from stimulus
Die out locally
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EM
(mV)
mV
-80
0
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EM
(mV)
mV
-80
0
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3. At some point, small increase in applied current triggers a membrane depolarization much greater than the stimulus current
Active response
ACTION POTENTIAL
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Characteristics of Action Potentials:
a. Minimum stimulus necessary to elicit
“threshold” current raises membrane to threshold potential
b. Once stimulated, all-or-none event
c. Propagated over long distances without decrement
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Characteristics of Action Potentials:
a. Minimum stimulus necessary to elicit
“threshold” current raises membrane to threshold potential
b. Once stimulated, all-or-none event
c. Propagated over long distances without decrement
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Characteristics of Action Potentials:
a. Minimum stimulus necessary to elicit
“threshold” current raises membrane to threshold potential
b. Once stimulated, all-or-none event
c. Propagated over long distances without decrement
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Characteristics of Action Potentials:
a. Minimum stimulus necessary to elicit
“threshold” current raises membrane to threshold potential
b. Once stimulated, all-or-none event
c. Propagated over long distances without decrement
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Characteristics of Action Potentials:
a. Minimum stimulus necessary to elicit
“threshold” current raises membrane to threshold potential
b. Once stimulated, all-or-none event
c. Propagated over long distances without decrement
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Characteristics of Action Potentials:
a. Minimum stimulus necessary to elicit
“threshold” current raises membrane to threshold potential
b. Once stimulated, all-or-none event
c. Propagated over long distances without decrement
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Characteristics of Action Potentials:
a. Minimum stimulus necessary to elicit
“threshold” current raises membrane to threshold potential
b. Once stimulated, all-or-none event
c. Propagated over long distances without decrement
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Characteristics of Action Potentials:
a. Minimum stimulus necessary to elicit
“threshold” current raises membrane to threshold potential
b. Once stimulated, all-or-none event
c. Propagated over long distances without decrement
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4. Voltage changes during action potentials
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4. Voltage changes during action potentials
EM
Time (msecs)
mVolts
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4. Voltage changes during action potentials
0
-20
-40
-60
-80
EM
Time (msecs)
mVolts
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4. Voltage changes during action potentials
EM
Time (msecs)0 1 2 3 4
mVolts
0
-20
-40
-60
-80
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4. Voltage changes during action potentials
EM
Time (msecs)0 1 2 3 4
mVolts
1. Resting membrane before arrival
1
0
-20
-40
-60
-80
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4. Voltage changes during action potentials
EM
Time (msecs)0 1 2 3 4
mVolts
2. Depolarization to 0 mV
1
20
-20
-40
-60
-80
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4. Voltage changes during action potentials
EM
Time (msecs)0 1 2 3 4
mVolts
2. Depolarization to 0 mV
hyperpolarizing overshoot
1
20
-20
-40
-60
-80
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4. Voltage changes during action potentials
EM
Time (msecs)0 1 2 3 4
mVolts
3. Repolarization back to -80 mV
1
2 30
-20
-40
-60
-80
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4. Voltage changes during action potentials
EM
Time (msecs)0 1 2 3 4
mVolts
4. Hyperpolarizing afterpotential
1
2 3
4
0
-20
-40
-60
-80
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4. Voltage changes during action potentials
EM
Time (msecs)0 1 2 3 4
mVolts
5. Return to resting
1
2 3
4 5
0
-20
-40
-60
-80