MEMBRANE POTENTIAL

Dr Onyango k
18/1/22
Objectives
 Concept of resting membrane potential (RMP)
 Explain the mechanism of genesis and maintenance of
RMP.
 Normal values of RMP of different excitable tissues and
equilibrium potential of important ions.
 Concept of Gibbs-Donnan Equilibrium.
 Concept of Nernst Equation
 Concept of Goldman-Hodgkin-Katz equation.
 Principle of recording of RMP.
Defn
 An electrical potential difference exists across the
membrane of all living cells with the inside being
negative in relation to the outside.
 This potential difference is called membrane potential
as ions arrange themselves along the outer and inner
surfaces of the cell membrane.
 At resting state of the cell, the membrane potential is
called resting membrane potential (RMP).
 RMP is also called transmembrane potential
 The RMP is different in different tissues .
 In a nerve cell, the RMP is –70 mV.
 When the neuron is stimulated, membrane potential changes and
inside of the cell becomes positive due to depolarization.
 The membrane potential during this state of activation is called
action potential.
 RMP plays an important role in deciding the degree and duration
of action potential, as the RMP is the level from where the phase
of depolarization starts.
 In some tissues like visceral smooth muscles, RMP is not stable
(fluctuates).
Tissue RMP
 Neuron –70 mV
 Skeletal muscle –90 mV
 Cardiac muscle –90mV
Contributors to RMP
 Selective permeability of the cell membrane to various
ions
 Gibbs-Donnan equilibrium
 Nernst equation
 Goldman-Hodgkin equation.
Membrane permeability
 The cell membrane is selectively permeable to ions and
other solute particles.
 Some ions are highly permeable, some are less
permeable and others are impermeable.
 The permeability mainly depends on the molecular
weight and the radius of ions in their hydrated form.
 Though the ions like Na+, K+, Cl– and HCO3– are
diffusible through the membrane, the permeability is
more for K+.
 Though the particle size of K+ is large as compared to
Na+ , the permeability for K+ is 500 to 1000 times
greater than that for Na+ for its effective radius.
 The membrane is practically impermeable to
intracellular proteins and organic phosphates.
Gibbs-Donnan Membrane
Equilibrium
 When two solutions containing ions are separated by a
semipermeable membrane, at equilibrium, each
solution will be electrically neutral.
 The total quantity of cations will be equal to total
quantity of anions.
 The product of diffusible ions on one side of the
membrane will be equal to product of diffusible ions on
the other side of the membrane.
 This is called Gibbs-Donnan membrane
equilibrium.
Donnan gibbs equilibrium
 There will be equal and balanced distribution of ions at
equilibrium.
 However, when non-diffusible ions is added on one side
,then as per Gibbs-Donnan equilibrium principle, the
distribution of diffusible ions will change to maintain
electroneutrality of both sides.
 ICF contains non-diffusible anions like proteins and
organic phosphate.
 Therefore, asymmetrical distribution of diffusible ions
occurs across the cell membrane with cations being
more inside than the outside.
 Therefore, at rest, interior of the cell is negative to the
exterior
Nernst Equation
 In accordance with Gibbs-Donnan equilibrium,
asymmetrical distribution of diffusible ions occurs
across the cell membrane with more cation (K+)
present inside.
 Therefore, K+ will try to diffuse into the ECF from ICF,
which is opposed by the electrical gradient, created by
presence of non-diffusible anions inside the cell.
 Thus, finally equilibrium is reached between the
concentration gradient and the electrical gradient
resulting in diffusion potential (equilibrium potential)
across the cell membrane.
Conc in mammalian motor neuron
ions ECF ICF EP(mV)
Na+ 150 15 +60
K+ 5.5 150 -90
Cl- 125 9 -75
HCO3- 21 5 -25
Calcium 2.5 10-4 +130
Goldman-Hodgkin-Katz Equation
 The magnitude of the membrane potential at any given
time depends on the distribution of Na+, K+ and Cl–
and on the permeability of each of these ions.
 The role of different ions in the generation of
membrane potential is accurately described by
Goldman-Hodgkin-Katz (GHK) equation or also
called Goldman’s constant field equation.
Importance of Goldman constant
equation
 Important ions that generate membrane potentials in
nerve and muscle fibers are sodium, potassium and
chloride.
 The voltage of membrane potential is determined by
the concentration gradient of each of these ions.
 The relativity of importance of each ion in
determination of the voltage depends upon the
membrane permeability of individual ion.
 Cation concentration from inside the membrane to
outside is responsible for electronegativity inside the
membrane.
RMP Genesis
 Resting membrane potential (RMP) is the membrane potential at rest.
 In neurons, the RMP is –70 mV
 Permeability of the membrane to K+: Normally, K+ is more inside and
less outside the cell.
 A concentration gradient exists for K+ from inside to outside that
facilitates K+ to diffuse out of the cell.
 At rest, permeability of the membrane to K+ is higher than any other ion.
 Therefore, K+ easily diffuses out of the cell, though this is opposed by the
electrical gradient.
 As, K+ is the major intracellular cation, its diffusion creates negativity
inside the cell.
 The permeability of the membrane to K+ is the major cause of RMP
 Permeability of the membrane to Na+: At rest, ECF
Na+ is more than the ICF Na+.
 There is a concentration gradient for Na+ from outside
to inside, for which Na+ diffuses into the cell.
 At rest membrane is less permeable to Na+ than to
K+.
 Therefore, K+ exit is not balanced by Na+ entry (more
K+ goes out).
 Hence, interior of the cell remains relatively negative.
 Permeability to anions:
 Exit of more cations from the cell should be
accompanied by proportionate exit of anion to maintain
electroneutrality.
 However, exit of K+ (the cation) is not accompanied by
exit of same amount of anions as permeability of
anions at rest is also not same as that of K+.
 Therefore, more negative ions remain inside.
 Role of Na+-K+ pump:
 The role of Na+-K+ pump is to maintain RMP rather
than to generate it.
 However, Na+-K+ pump also contributes to the genesis
of RMP, as it is an electrogenic pump.
 It pumps out three Na+ for two K+ to come in.
 Therefore, it pumps more cations out of the cell and
less into the cell.
 Thus, less cations are taken inside, which in other
words, a relatively negativity is created inside
Maintenance of RMP
 K+ diffusing out of the cell and Na+ diffusing into the
cell will come to halt once the concentration gradient
ceases to exist for both the ions.
 However, that does not happen, as Na+-K+ ATPase
helps in building the concentration gradient.
 It serves to pump back the Na+ that diffuses into the
cell and K+ that diffuses out of the cell.
 Thus, Na+-K+ pump plays an important role in
maintaining RMP
Recording RMP
 The membrane potential is recorded like recoding of
activity of any excitable tissue.
 This requires:
 Microelectrodes
 Electronic amplifiers
 Cathode ray oscilloscope (CRO).
Principle of RMP recording
 Two microelectrodes are placed on the surface of a
nerve fiber and connected to a CRO.
 When, one of the microelectrodes is inserted inside the
nerve fiber, a steady potential difference of –70 mV
(inside negative) is observed on the CRO .
 This is the recording of membrane potential and
indicates the resting state of the neuron.
 This can be recorded from any cell in the body in the
state of polarization.