1. DIFFUSION POTENTIAL, RESTING MEMBRANE POTENTIAL, AND ACTION POTENTIAL

2. Ion channels
are integral proteins that span the membrane and, when open, permit the passage of certain ions.
Ion channels are selective
2. Ion channels may be open or closed.
3. The conductance of a channel depends on the probability that the channel is open.
. Ion channels are selective; they permit the passage of some ions, but not others. Selectivity is based on the size of the channel and the distribution of charges that line it.
2. Ion channels may be open or closed. When the channel is open, the ion(s) for which it is selective can flow through. When the channel is closed, ions cannot flow through
The higher the probability that a channel is open, the higher the conductance, or permeability. Opening and closing of channels are controlled by gates.

3. Voltage-gated channels
Open or close by changes in membrane potential.
The activation gate of the Na+ channel in nerve is opened by depolarization; when open, the nerve membrane is permeable to Na+ (e.g., during the upstroke of the nerve action potential).
The inactivation gate of the Na+ channel in nerve is closed by depolarization; when closed, the nerve membrane is impermeable to Na+ (e.g., during the repolarization phase of the nerve action potential).

5. Ligand-gated channels
are opened or closed by hormones, second messengers, or neurotransmitters.
For example, the nicotinic receptor for acetylcholine (ACh) at the motor end plate is an ion channel that opens when ACh binds to it. When open, it is permeable to Na+ and K+, causing the motor end plate to depolarize.

6. The concept of a steady state.
The concept of a steady state. Na enters a
cell through nongated Na channels, moving
passively down the electrochemical gradient. The rate of Na entry
is matched by the rate of active transport of Na out of the
cell via the Na/K-ATPase. The intracellular concentration of
Na remains low and constant. Similarly, the rate of passive K
exit through nongated K channels is matched by the rate of active
transport of K into the cell via the pump. The intracellular
K concentration remains high and constant. During each cycle
of the ATPase, two K are exchanged for three Na and one
molecule of ATP is hydrolyzed to ADP. Large type and small
type indicate high and low ion concentrations, respectively.

7. IONIC COMPOSITION OF BODY FLUIDS
Ions constitute 95% of solutes
Na+,Ca2+, Cl-, &HCO3– largely extracellular
K+, Mg2+, organic phosphates,& protiens – predominently present in ICF
Sum of conc of cations = Sum of conc of anions

9. Bioelectric potentials
Exists between interior and exterior of all cell membrane of the living body
Generated by charged ions lining the either side of the cell membrane
No potential difference deep in the cytoplasm

10. Diffusion potentials
A diffusion potential is the potential difference generated across a membrane because of a concentration difference of an ion.
A diffusion potential can be generated only if the membrane is permeable to the ion.
The size of the diffusion potential depends on the size of the concentration gradient.

11. Diffusion potentials
The sign of the diffusion potential depends on whether the diffusing ion is positively or negatively charged.
Diffusion potentials are created by the diffusion of very few ions and, therefore, do not result in changes in concentration of the diffusing ions.

12. Example of a Na+ diffusion potential
As a result, a diffusion potential will develop and solution 1 will become negative with respect to solution 2.
. Eventually, the potential difference will become large enough to oppose further net diffusion of Na+. The potential difference that exactly counterbalances the diffusion of Na+ down its concentration gradient is the Na+ equilibrium potential.
At electrochemical equilibrium, the chemical and electrical driving forces on Na+ are equal and opposite, and there is no net diffusion of Na

13. Equilibrium potentials
The equilibrium potential is the diffusion potential that exactly balances (opposes) the tendency for diffusion caused by a concentration difference.
At electrochemical equilibrium, the chemical and electrical driving forces that act on an ion are equal and opposite, and no more net diffusion of the ion occurs.

14. Example of a Cl- diffusion potential
A diffusion potential will be established such that solution 1 will become positive with respect to solution 2. The potential difference that exactly counterbalances the diffusion of Cl- down its concentration gradient is the Cl- equilibrium potential. At electrochemical equilibrium, the chemical and electrical driving forces on Cl- are equal and opposite, and there is no net diffusion of Cl-.

15. Role of Na+ & K+ leak channels
Exceedingly important
100 times more permeable to potassium

16. Nernst equation Membrane potential can be predicted theoretically from the concentration of ions on either side of the cell membrane after equilibrium (Diffusion potential )

17. ESTABLISHMENT OF DIFFUSION POTENTIALS

18. Nernst potential Diffusion Potential for single ion;
Nernst potential - The diffusion potential level across a membrane that exactly opposes the net diffusion of a particular ion through the membrane is called the Nernst potential for that ion.
conc. Inside
E M F (mv) = ± 61 log
conc. Outside
The Nernst equation is used to calculate the equilibrium potential at a given concentration
difference of a permeable ion across a cell membrane. It tells us what
potential would exactly balance the tendency for diffusion down the concentration
gradient; in other words, at what potential would the ion be at electrochemical
equilibrium

20. These are the most common forms of the Nernst equation in use
These are the most common forms of the Nernst equation in use. By inspection of these equations it is apparent that for a univalent ion (e.g., Na+, K+, Cl-), a 10-fold concentration gradient across the membrane is equivalent in energy to an electrical potential difference of 61.5 mV and a 100-fold gradient is equivalent to 123 mV. Similarly, for a divalent ion (e.g., Ca++), a 10-fold concentration gradient is equivalent to a 30.7-mV electrical potential difference because z in the above equations is equal to 2.

21. Q
If the intracellular [Na+] is 15 mM and the extracellular [Na+] is 150 mM, what is the equilibrium potential for Na+?

22. Solutions A and B are separated by a membrane that is permeable to Ca2+ and impermeable to Cl-. Solution A contains 10 mM CaCl2, and solution B contains 1 mM CaCl2. Assuming that 2.3 RT/F = 60 mV, Ca2+ will be at electrochemical equilibrium when
(A) solution A is +60 mV
(B) solution A is+30 mV
(C) solution A is -60 mV
(D) solution A is -30 mV
(E) solution A is +120 mV
(F) solution A is -120 mV
(G) the Ca2+ concentrations of the two solutions are equal
(H) the Cl- concentrations of the two solutions are equal

23. Nernst potential Diffusion potential / equilibrium potential )
The potential level across the membrane that exactly opposes net diffusion of a particular ion through the membrane
EMF ( electromotive force ) =
+ 61 log conc. inside / conc. outside
Potassium (Ek) = millivolts (negativity inside)
Sodium (ENa) = + 61 millivolts (positivity inside )
Chloride (Ecl) = millivolts (nerve fiber)
= millivolts (muscle fiber)

24. GOLDMAN – HODGKIN KATZ EQUATION
For several ions
C Na+i PNa+ + Ck-I PK CCl_ o PCl_
E M F = - 61 log
C Na+o PNa+ + Ck-o PK CCl_ i PCl_
 Depends on permeability , polarity and concentration inside & outside.
R . M . P of Nerves : - 90mV
Na⁺o : 142 mEq/L
Na⁺i : mEq/L
K⁺o : mEq/L
K⁺I : 140mEq/L
Ratio given inside to outside are:
Na ⁺inside / Na ⁺outside = 0.1
K⁺ inside / K⁺outside = 35.0
(II) Leakage of K⁺ Na⁺ : K⁺ is 100 times more permeable.

25. Role of sodium potassium pump
Electrogenic pump
Pumps 3 Na+ outside
Pumps 2 K+ inside
Creates more negativity
inside

26. CHARACTERISTICS OF NA – K PUMP

27. RESTING MEMBRANE POTENTIALS
Caused by :
(a) Diffusion potential
(b) Na⁺ - K⁺ pump
(C) K⁺ - Na⁺ leak channels S

28. Development of RMP
Efflux of K+ leads to a diffusion potential which is mainly responsible for the RMP with inside negative
1. K+ permeability is far more than Na+ through the resting membrane (-84mv)
2. High intracellular K+ is due to activity of the Na+ K+ pump (- 4mv )
3. K⁺ - Na⁺ leak channels
4. Impermeability of Proteins (Intracellular anions )
RMP is defined as being negative
Varies between –9mV to -90mV

29. ORIGIN OF THE NORMAL R .M .P
1. Contribution of K
According to Nernst equation it is mV.
Log of 35 is 1.54
61 × 1.54 = - 94 mV
2. Contribution of Na
R M P will be +61mV
Log 0.1 is – 1
61 × -1 = +61 mV
3. When both are calculated together
By Goldman equation it is – 86 mV.
II Contribution of Na⁺ K⁺ pump: is – 4 mV

30. Measurement of RMP RMP of smooth muscle= -50mv
RMP of SA nodal cells = -60 mv
RMP of nerve fibres = -70 mv
RMP of RBC = - 9 mv

31. ESTABLISHMENT OF RESTING MEMBRANE POTENTIAL