Definition of excitable cells - Cells which are capable of generation and  However if there is animpermeable solute in one of the

one of the solutions, the

transmission of electrochemical impulses along the membrane concentration of the solution does not equalize.
Excitable  The concentration ofthe solution with impermeable solutesremains
1. Nerve Non-excitable cells
high even at equilibrium. This effect is called the Gibbs-Donnan
2. Muscle 1. RBC
equilibrium
• Skeletal 2. Intestinal cells
 There is unequal distribution of diffusible ions in one of the solutions,
• Cardiac 3. Fibroblasts
the concentration of the solution does not equalize.
• Smooth 4. Adipocytes
 Since ICF contains non diffusible anions ie proteins and organic PO42-,
 All cells are separated from their environment by their plasma membrane there is unequal distribution of diffusible ions across the cell, with more
 Plasma membrane is a phospholipid bilayer, with a phosphate head and a cations inside the cell.
fattyacid tail
 Because it contains lipid, the plasma membrane has a low intrinsic permeability 3. Nernst equation
 However, certain molecules embedded in the membrane are capable of actively  The unequal distribution of diffusible ions due to Gibbs-Donnan
transporting ions across the membrane or providing channels for their equilibrium result in a concentration gradient
movement  So diffusible ions will try to diffuse but it is counteracted by the
 The membrane is thus selectively permeable to ions. This leads an unequal electrical gradient
distribution of charged ions (membrane potential difference) across the two sides  An equilibrium will be reached between the concentration gradient and
of the membrane electrical gradient resulting in diffusion potential (equilibrium
 there is an electrical potential difference between the inside of the cell and the potential) across the cell membrane.
ECF. This potential difference is referred to as the membrane potential (Vm)  The Nernst equation calculates the equilibrium potential (= Nernst
 The membrane potential at rest is called the Resting Membrane Potential (RMP) potential) for an ion based on the charge of the ion (= its valence) and
 RMP is an equilibrium situation where thedriving force for diffusible ions down its concentration gradient across the membrane
their concentration gradient = and oppose the driving force for these ions down  Equilibrium potential (Veq) for an ion is the membrane potential
their electrical gradient whereby the force due to the electrical gradient is equal to
 Does not mean that the cell is metabolically inactive concentration gradient of that ion until there is no net movement of
 If measured with a voltmeter the intracellular compartment is slightly negative that ion
compared to the extracellular compartment

RMP IN DIFFERENT CELLS

 The RMP in body cells varies from (-) 5mV to (-) 100 mV
 In a nerve cell the RMP is about (-) 70 mV
 In a muscle cell the RMP is about (-) 90 mV
 The membrane potential measured during the excited state of the cell is
called action potential.
GENESIS OF MEMBRANE POTENTIAL
 Membrane potential is due to unequal distribution of ions across cells
 Since VCl = Vm, there are no other
 Membrane potential results from the combined effects of variousforces forces other than chemical gradient
acting on the ions and electrical gradient which
GENESIS OF MEMBRANE POTENTIAL determine the distribution of Cl-
Important factors involved in the genesis of across membrane.
membrane potential are :
1. Selective permeability of the cell membrane 4. Goldman-Hodgkins-Katz
2. Gibbs-Donnan equilibrium equation
3. Nerst equation 5. Na+-K+ ATPase pump

1. Selective permeability of the cell membrane

 Na+,K+, Cl- and HCO3 are diffusible ions
 Cell membrane is freely permeable to K+ and Cl- but moderately permeable to Na+
 K+ is approx 50-100x > permeable than Na+
 Cell membrane is practically impermeable to intracellular proteins and organic
 VK = -90 mV whereas Vm = -70 mV
PO42-
 VK ≠ Vm
 Variable ionic permeability is due to thepresence of gated channels in the cell
 Therefore there are other forces besides chemical and electrical
membrane
gradient which causes the excess of K+ inside the cell.
 That force is Na+-K+ ATPase. It is to ensure
2. Gibbs-Donnan equilibrium
[K+]i > [K+]o
In membrane equilibrium, when two ionized VKand VNa ≠ Vm
solutions are separated by a semi permeable  If the forces that act on the
membrane: membrane are only chemical and
 Each solution will be electrically neutral. Total charges cation = total charges anions electrical gradients, it is assumed
 The products of diffusible ions in both solutions will be equal that the cell will eventually gain
 Their concentrations will equalize as a result of diffusion. Na+ and lose K+ by diffusion
 However, in reality, the
concentration of Na+ and K+ in
the cell is constant, due to the
presence of Na+-K+
 ATPase and also due to
impermeability of membrane
towards Na+
4. Goldman-Hodgkins-Katz equation EFFECTS OF CHANGES INEXTRACELLULAR NA+ AND K+
 The integrated role of different ions in the generation of membrane potential CONCENTRATIONS ON RMP
can be calculated using the Goldman-Hodgkin-Katz (GHK) Equation:

EFFECT OF SUDDEN HYPERKALEMIA ON RMP

Inferences that can be drawn from the GHK equation:

1. Most important ions for development of membrane potentials in nerve and

muscle fibers are Na+, K+, Cl-

2. Degree of importance of each ion is depends on membrane permeability of

the individual ion. e.g. if membrane is NOT permeable to K + and Cl-,then the
membrane potential will be determined by Na+ gradient alone (= Nerst
potential for Na+)

3. Positive ion concentration is responsible for electronegativity inside the

membrane. Because of the concentration gradient, the positive ions diffuse
outside leaving non-diffusible negative ions inside the cell.

4. Signal transmission in the nerves is primarily due to the change in Na+ and
K+ permeability because their channels undergo rapid change during
conduction of the nerve impulse. Not much change is seen in the Cl- channels.

5. Na+-K+ ATPase pump

 Builds the concentration gradient

 Pumps back Na+ that diffuse into the cell and K+ that diffuses out.
 In the resting membrane these diffusions are negligible, so the Na+-K+
ATPasepump works feebly.
 Although the pump is potentially electrogenic (pumps out 3 Na+ and pumps
in 2 K+), it is notable to build up a significant membranepotential. Why?
 As soon as the pump create a negative potential inside the cell, Cl rush out
ofthe cell and restore neutrality.