CONCEPT OF NERST POTENTIAL AND SODIUM POTASSIUM PUMP BY: DR.ANEEQA SHAHID

ECF and ICF

ECF and ICF

Molecular Gradients inside outside 14 142 140 4 0.5 1-2 Na+ 10-4 K+ (in mM) 14 140 0.5 10-4 (pH 7.2) 10 5-15 2 75 40 outside (in mM) 142 4 1-2 (pH 7.4) 28 110 1 5 Na+ K+ Mg2+ Ca2+ H+ HCO3- Cl- SO42- PO3- protein

Types of Transport Passive and Active Passive Simple Diffusion Facilitated Diffusion Active Primary Co-Transport Counter Transport Secondary The lipid barrier and transport proteins Transport proteins Carreir Channel

Transport Passive Transport (Diffusion) (Kinetic energy only) Random molecular movement of substances molecule by molecule, either through intermolecular spaces in membrane or in combination with a carrier protein Active Transport (Kinetic + Additional Energy for movement) Movement of ions or other substances across the membrane in combination with a carrier protein that can cause the substance to move against an energy gradient (as from low to higher concentration)

Basic Mechanisms of Transport

Molecular Gradients inside outside 14 142 140 4 0.5 1-2 Na+ 10-4 K+ (in mM) 14 140 0.5 10-4 (pH 7.2) 10 5-15 2 75 40 outside (in mM) 142 4 1-2 (pH 7.4) 28 110 1 5 Na+ K+ Mg2+ Ca2+ H+ HCO3- Cl- SO42- PO3- protein

Simple Diffusion inside outside K+ Na+

- charge difference across the membrane - Membrane Potential (Vm): - charge difference across the membrane - inside outside …how can passive diffusion of potassium and sodium lead to development of negative membrane potential? K+ K+ Na+ Na+

Basic Physics of Membrane Potentials Membrane Potential Caused by Diffusion Diffusion Potential When equilibrium established Equilibrium potential Assuming freely permeable membrane for one ion at a time

Simplest Case Scenario: inside outside If a membrane were permeable to only K+ then… K+ K+ would diffuse down its concentration gradient until the electrical potential across the membrane countered diffusion. K+ The electrical potential that counters net diffusion of K+ is called the K+ equilibrium potential (EK).

K conductance

Simplest Case Scenario: inside outside If a membrane were permeable to only Na+ then… Na+ Na+ would diffuse down its concentration gradient until potential across the membrane countered diffusion. Na+ The electrical potential that counters net diffusion of Na+ is called the Na+ equilibrium potential (ENa).

Na Conductance

Nernst Equation Relation of diffusion potential to the concentration difference…… resulting in Nernst (equilibrium) potential For any univalent ion at body temperature of 37° C EMF (mV)= +/-61log (Conc.inside/Conc.outside) Calculate for K+ and Na+ K= -61log(140/4) Na= -61log(14/142) Sign is –ve for +ve ion and vice versa

The Potassium Nernst Potential …also called the equilibrium potential EK = 61 log   Ki Ko Example: If Ko = 5 mM and Ki = 140 mM EK = -61 log(140/4) EK = -61 log(35) EK = -94 mV So, if the membrane were permeable only to K+, Vm would be -94 mV

The Sodium Nernst Potential Nai Nao EK = 61 log   Example: If Nao = 142 mM and Nai = 14 mM EK = -61 log(14/142) EK = -61 log(0.1) EK = +61 mV So, if the membrane were permeable only to Na+, Vm would be +61 mV

NOW CONCENTRATE further

Role of multiple ions

Multiple ions and diffusion potential 3 factors Polarity of each ion Membrane permeability of the ions Concentrations of respective ions on both sides: (i= inside), (o= outside)

. . The Goldman-Hodgkin-Katz Equation p V ] [ ' log = 61 p V ] [ ' log (also called the Goldman Field Equation) Calculates Vm when more than one ion is involved. o Cl i Na K m p V ] [ ' log . - + = 61 i Cl o Na K m p V ] [ ' log . - + = -61 or Cl ions are distributed across the membrane in accordance with their equilibrium potential – when Vm changes, Cl ions redistribute themselves in accordance to the new Vm, i.e., Eq Cl = Vm. Cell membranes of muscles have Cl permeability equal to or greater than that of K. NOTE: P’ = permeability

Multiple Channels

K+ Na+ Active Transport inside outside Na+ K+ 3 Na+ 2 K+ ATP K+ 3 Na+ 2 K+ ADP Remember: sodium is pumped out of the cell, potassium is pumped in...

PRIMARY ACTIVE TRANSPORT Sodium-potassium pump It pumps sodium ions out of the cell and potassium ions into the cell. The pump contains a carrier protein which is a complex of two separate globular proteins, a larger one called the α-subunit (mol. wt.= 100,000) and a smaller one called the β-subunit (mol. wt.=55,000)

The smaller subunit anchors the protein complex lipid membrane, while the larger one has three important features: It has three receptor sites for binding Na+ on the inside of the cell It has two receptor sites for K+ on the outside of the cell. Inside of the protein near the binding site of Na+ has ATPase activity.

Na+ K+ PUMP

When two potassium ions bind on the outside of the carrier protein and three sodium ions bind to the interior, the ATPase function of the carrier protein is activated. This cleaves one molecule of ATP, with the liberation of high energy phosphate bond. This energy brings a chemical and conformational change in the carrier protein molecule, extruding Na+ to outside and K+ to inside of the cell.

Functions of Na+/K+ pump It establishes a Na+/K+ concentration difference across the cell membrane and makes a –ve electrical voltage inside the cell. It regulates the cell volume by controlling the concentration of solutes. Thus, prevent the swelling or shrinking of the cell. The energy stored during the transport of Na+/K+ is used for secondary active transport.

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