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a, b, c, d all move solutes by diffusion down concentration gradient. Final mechanism can work against gradient e. Active transport. Final mechanism can work against gradient e. Active transport. XXX XX XXX. X. Final mechanism can work against gradient e. Active transport.
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a, b, c, d all move solutes by diffusion down concentration gradient
Final mechanism can work against gradient • e. Active transport
Final mechanism can work against gradient • e. Active transport XXX XX XXX X
Final mechanism can work against gradient • e. Active transport XXX XX XXX X
Final mechanism can work against gradient • e. Active transport Pump Protein XXX XX XXX X
Final mechanism can work against gradient • e. Active transport XXX XX XXX X
Final mechanism can work against gradient • e. Active transport ATP XXX XX XXX X
Final mechanism can work against gradient • e. Active transport ATP XXX XX XXX X ADP + Pi
Final mechanism can work against gradient • e. Active transport XXX XX XXX X
Final mechanism can work against gradient • e. Active transport XXX XXX XXX Concentrates against gradient
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
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
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....
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+
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
Permeable uncharged solutes will come to equilibrium across membranes if no other forces acting
Permeable uncharged solutes will come to equilibrium across membranes if no other forces acting 1 M sucrose
Permeable uncharged solutes will come to equilibrium across membranes if no other forces acting 1 M sucrose
Permeable uncharged solutes will come to equilibrium across membranes if no other forces acting 1 M sucrose 0.5 M sucrose 0.5 M sucrose
Permeable charged solutes will not come to concentration equilibrium across membrane if other charged impermeable solutes are present
Na+ A- Impermeable
K+ Cl- Na+ A- Permeable
K+ Cl- Na+ A-
K+ Cl- Na+ A-
K+ Cl- Cl- Na+ Na+ A- A- K+
K+ Cl- • At equilibrium: chemical force driving K+ out Cl- Na+ Na+ A- A- K+
K+ Cl- • At equilibrium: chemical force driving K+ out • is exactly balanced by the electrical force (electromotive force) holding K+ in Cl- Na+ Na+ A- A- K+
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 Cl- Na+ Na+ A- A- K+
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” Cl- Na+ Na+ A- A- K+
Donnan Equilibrium resembles situation in real cell, with one exception: • cell is not maintained passively • Poison real cell and unequal distribution eventually goes away
c. Cells work via pumps to maintain unequal ion distribution • Na+ “leaks” in down chemical and electrical gradients
c. Cells work via pumps to maintain unequal ion distribution • Na+ “leaks” in down chemical and electrical gradients Na+ A-
c. Cells work via pumps to maintain unequal ion distribution • Na+ “leaks” in down chemical and electrical gradients Na+ A-
c. Cells work via pumps to maintain unequal ion distribution • Na+ “leaks” in down chemical and electrical gradients Na+ Na+/K+ ATPase Na+ A-
c. Cells work via pumps to maintain unequal ion distribution • Na+ “leaks” in down chemical and electrical gradients Na+ Na+ A-
c. Cells work via pumps to maintain unequal ion distribution • Na+ “leaks” in down chemical and electrical gradients Na+ K+ Na+ A-
c. Cells work via pumps to maintain unequal ion distribution • Na+ “leaks” in down chemical and electrical gradients Na+ Na+ K+ A-
c. Cells work via pumps to maintain unequal ion distribution • Na+ “leaks” in down chemical and electrical gradients Na+ Na+ K+ A- If Na+ allowed to build up, inside becomes + , drives K+ out, and lose unequal distribution
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)
2. Membrane potential measurement • a. Voltmeter
2. Membrane potential measurement • a. Voltmeter
2. Membrane potential measurement • a. Voltmeter
2. Membrane potential measurement • a. Voltmeter
2. Membrane potential measurement • a. Voltmeter Inside is -80 mV
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
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
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
d. CONCLUSION: • In ion mixture, each ion contributes to the overall EM in proportion to its permeability • Most permeable ions contribute the most charge
Which ion is most permeable? • K+ • real cell: inside is -80 mV = resting EM • cell is “negatively polarized”
EM is due almost exclusively to the unequal distribution of K+ • Changes in [K+] alter EM easily • Changes in [Na+] do not alter EM