Resting Membrane Potential
Uneven Distribution of Solutes Amongst Body
Compartments
F5-28
•Cell membranes prevent most solutes from diffusing amongst compartments.
Solutes are molecules which dissolve in liquid.
• Active transport of solutes helps create and maintain differences in solute
concentrations.
• The body is kept in a state of chemical disequilibrium.
Water Distribution Throughout the Body Affects
Solute Concentration
• Women have less water (esp. in 17-39 yr olds) than men because they have
more adipose (fat) tissue; large fat droplets occupy most of the cell, and thereby
reduce the water content of the cytosol.
•In clinical practice, the body’s water content needs to be taken into
consideration when drugs are prescribed. Eg. since women and older people
have less water than young men, the drug concentration in plasma will be
higher in them than young males if administered equal drug dose per kg.
Distribution of Water in the Body: Osmosis
Membrane permeable to water
Osmotic
Pressure
• In osmosis, water moves to dilute the area of more concentrated solute. In other
words, water moves down its concentration gradient.
•Osmosis stops when the concentration of solute is equal in each compartment. In
other words, water moves freely between compartments until its distribution is
equal. The equal distribution of water is known as osmotic equilibrium.
•The compartments of our body are in osmotic equilibrium.
• Osmotic pressure is the pressure applied to stop osmosis.
F5-29
Osmolarity
•Determining the concentration of the solutions in different compartments
will indicate whether osmosis can takes place. Water moves into the
compartment of higher solute concentration.
•Definition: Measure of the number of solute particles in a given volume
of solution (osmol/L). This is different to molarity (mol/L) which measures
the number of molecules per given volume of solution.
•Concentration in osmosis is concerned with the number of particles,
rather than with the number of molecules in a given volume of solution,
since water moves osmotically in response to the total concentration of
particles in solution. Eg.one molecule of glucose yields one particle when
dissolved in water, whereas NaCl yields two particles; namely, Na+ and Cl-
•Conversion of molarity (M) into osmolarity (OsM): Molarity * (# of
particles/ molecule in solution)
•Osmolarity of the human body can range from 280-296 mOsM.
Comparison of Osmolarities Between Two
Solutions
•Isosmotic = If two solutions have the same number solute particles per unit
volume.
•If the osmolarity of solution A is greater than in solution B, we say that A is
hyperosmotic to solution B, whereas solution B is hyposmotic to solution A.
• Compartments of the body are in a state of osmotic
equilibrium but in a state of chemical and electrical
disequilibrium.
• The electrical disequilibrium (resulting from
separation of charge across the membrane) is of prime
importance to electrical signalling in nerve and muscle.
Uneven Distribution of Major Ions in the
Intracellular and Extracellular Compartments
(mM)
Ion
K+
Na+
ClOrganic
Anions
Intracellular Extracellular Normal
Plasma
Value
150
5
3.5-5.0
12
140
135-145
10
105
100-108
65
0
T5-9
• The body is in a state of electrical disequilibrium because active transport of
ions across the cell membrane creates an electrical gradient.
• Although the body is electrically neutral, cells have excess negative ions on the
inside and their matching positive ions are found on the outside.
Electricity Review
• A) Law of conservation of charge: the net amount of electric
charge produced in a system is zero. ie. for every +ve charge on
an ion, there is an electron on another ion. Overall, the body is
electrically neutral.
• B) Opposite charges attract and like charges repel.
• C) Energy is needed to separate charge.
• D) If separated charges could move towards one another, the
material through which they are moving is called a conductor.
• E) If the material prevents the movement of separate charges, the
material is called an insulator. The cell membrane is a good
insulator.
• Static electricity arises from the separation of electric charge.
Separation of Electric Charge Across the Cell
Membrane
• The
system is in
chemical, electrical and
osmotic equilibrium.
• The
system is in
osmotic equilibrium,
but chemical and
electrical
disequilibrium.
F5-31
Electrochemical Gradient
•The input of energy to
transport ions across a
membrane has created an
electrical gradient.
•The active transport of
positive ions out of the cell has
created a chemical gradient.
The combination of an
electrical and chemical
gradient is called an
electrochemical gradient.
•However, the cell remains in
osmotic equilibrium.
• The -ve ion will try and move down the
electrical gradient and follow the +ve ion
out of the cell, but the membrane inhibits
its flow as it’s a good insulator.
• Physiological measurements
are carried out on a relative
scale.
Resting Membrane Potential (Difference)
• The resting membrane potential is the electrical gradient across the
cell membrane.
• Resting: the membrane potential has reached a steady state and is not
changing.
• Potential: the electrical gradient created by the active transport of
ions is a source of stored or potential energy, like chemical gradients
are a form of potential energy. When oppositely charged molecules
come back together again, they release energy which can be used to do
work (eg. molecules moving down their concentration gradient).
• Difference: the difference in the electrical charge inside and outside
the cell (this term is usually omitted)
Measuring the Resting Membrane Potential
•It is measured with glass
micropipets filled with solutions
which conduct charge. The
micropipet is inserted through the
membrane into the cell.
• The voltmeter measures the
difference in electrical charge
between two points, in other words,
the potential difference; it is
measured in millivolts (mV).
• The resting membrane potential is measured on a relative scale.
• The reference electrode is placed in the extracellular fluid. The extracellular
fluid is designated as the ground and assigned a charge of 0 mV. In reality, the
extracellular fluid is not neutral and has an excess of +ve charge that balances
the excess of -ve charge in the cell.
• The resting membrane potential is between -40 to -90 mV in nerve and
muscle.
F5-32
K+ Ions Contribute to the Resting Membrane
Potential
• In electrical equilibrium and chemical disequilibrium.
• Membrane is more permeable to K+ ions.
• K+ leaks out of the cell down its concentration gradient.
• Excess -ve charge buildup inside the cell as Pr- cannot
cross the membrane. An electrical gradient is formed.
• The -ve charges attract K+ ions back into the cell down
the electrical gradient.
• Net movement of K+ stops. The membrane potential at
which the electrical gradient opposes the chemical
gradient is known as the equilibrium potential (E). EK= 90 mV.
F5-33
Nerst Equation
• The equilibrium potential is calculated using the Nerst equation:
RT [I]out
Eion 
ln
Fz [I]in
(mV)
• Derived under resting membrane conditions when the work required to move
an ion across the membrane (up its concentration gradient) equals the electrical
work required to move an ion against a voltage gradient.
R= gas constant (8.314 jules/oK.mol)
T= temperature (oK)
F= Faraday constant (96, 000
coulombs/mol)
z= the electric charge on the ion
[I]out= ion concentration outside the cell
[I] in= ion concentration inside the cell
Contribution of Na+ to the Resting Membrane
Potential
• Membrane permeable to Na+ only.
• Same principles hold as in the case of K+ movement across the membrane.
• The equilibrium potential for Na+ is, ENa= +60 mV.
F5-34
Resting Membrane Potential in Real Cells
• Most cells are 40x more permeable to K+ than
Na+. As a result, the resting membrane potential is
much closer to EK than ENa.
• In actual cells, the resting membrane potential is
much closer to -70 mV because a small amount of
Na+ leaks into the cell.
• The Na+ is pumped out and the K+ pumped in by
the Na+/K+-ATPase. It pumps 3 Na+ ions out and 2
K+ ions in.
• Na+/K+-ATPase is also known as an electrogenic pump because it helps maintain
an electrical gradient.
• Not all transporters are electrogenic pumps:
•Na+/K+/2Cl- symporter moves one +ve charge for every -ve charge.
• HCO3-/Cl- antiport in red blood cells moves these ions in a one-for-one
fashion.
F5-35
Goldman Equation
• It is used to calculate the membrane potential resulting from all the
participating ions when Vm is not changing:



RT PK [K ]out  PNa [Na ]out  PCl [Cl ]in
Vm 
ln
zF PK [K  ]in  PNa [Na  ]in  PCl [Cl ]out
• PX= the relative permeability of the membrane to ion X (measured
in cm/s). An ion’s contribution to the membrane potential is
proportional to its ability to cross the membrane.
• PK: PNa: PCl= 1.0: 0.04: 0.45 at rest.
References
1.
Tortora, G.J. & Grabowski, S.R (2003). Principles of
Anatomy & Physiology.New Jersey: John Wiley & Sons.
Ch.12, pp.396-398.
2.
Silverthorn, D.U (1998). Human Physiology: An
Integrated Approach. New Jersey: Prentice Hall. Ch.5,
pp.131-133, 136-141.
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