DIFFUSION POTENTIAL, RESTING MEMBRANE POTENTIAL, AND ACTION POTENTIAL

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.

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).

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.

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.

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

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

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.

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.

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

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.

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-.

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

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

ESTABLISHMENT OF DIFFUSION POTENTIALS

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

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.

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

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

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) = - 94 millivolts (negativity inside) Sodium (ENa) = + 61 millivolts (positivity inside ) Chloride (Ecl) = - 70 millivolts (nerve fiber) = - 90 millivolts (muscle fiber)

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 : 14 mEq/L K⁺o : 4 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.

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

CHARACTERISTICS OF NA – K PUMP

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

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

ORIGIN OF THE NORMAL R .M .P 1. Contribution of K According to Nernst equation it is - 94 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

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

ESTABLISHMENT OF RESTING MEMBRANE POTENTIAL