RESTING MEMBRANE POTENTIAL Presents to you by ABOUT DISEASE.CO TEAM

OBJECTIVES By the end of this lecture, you should be able to: Define Nernst potential. Use the Nernst equation to calculate the values of Nernst potential for Na, K & Cl. Define Resting Membrane Potential. Give the physiological basis of Resting membrane potential. Use the Nernst equation and Goldmann-Hoghkin-Katz equation to calculate the RMP. Explain the contribution of Sodium-Potassium Pump to the RMP.

Points to Note: Opposite charges (– and +) are attracted to each other, but two charges of the same type (– and –, or + and +) repel each other. A concentration gradient can exist for molecules/ particles and ions. A CHEMICAL gradient can exist in the presence of an ELECTRICAL gradient.

SEMIPERMEABLE MEMBRANE This diagram shows the membrane as being SEMI-PERMEABLE... Which means that it is selectively permeable to some ions/molecules and not to others....

If the membrane is impermeable or semi-permeable, THEN, How do we make it selectively permeable to a specific ion?

The ion channels can be of 2 main types: The Role of Channels The ion channels can be of 2 main types: Leak channels: Include ion channels specific for Na+, K+, Cl- etc. As long as the size of the ion is appropriate, the ion will go through them. 2. Gated channels: The gates are part of the protein channel and can open or close in response to certain stimuli. Ligand Gated Channels Voltage Gated Channels

MEMBRANE POTENTIAL :

Measuring the Resting Membrane Potential Electrodes are created from hollow glass tubes drawn to very fine points. These micropipettes are filled with a liquid that conducts electricity and then connected to a voltmeter, which measures the electrical difference between two points in units of either volts (V) or millivolts (mV). A recording electrode is inserted through the cell membrane into the cytoplasm of the cell. A reference electrode is placed in the external bath, which represents the extracellular fluid. When the recording electrode is placed inside a living cell, the voltmeter measures the membrane potential, in other words, the electrical difference between the intracellular fluid and the extracellular fluid. Electrodes are created from hollow glass tubes drawn to very fine points. These micropipettes are filled with a liquid that conducts electricity and then connected to a voltmeter, which measures the electrical difference between two points in units of either volts (V) or millivolts (mV). A recording electrode is inserted through the cell membrane into the cytoplasm of the cell. A reference electrode is placed in the external bath, which represents the extracellular fluid. When the recording electrode is placed inside a living cell, the voltmeter measures the membrane potential, in other words, the electrical difference between the intracellular fluid and the extracellular fluid.

Separation of Charges is called Membrane Potential

It is the separation of charges across the membrane. MEMBRANE POTENTIAL DEFINITION: It is the separation of charges across the membrane. OR It is the difference in the relative number of cations & anions in the ICF & ECF. The resting part of the name comes from the fact that this electrical gradient is seen in all living cells, even those that appear to be without electrical activity. In these resting cells, the membrane potential has reached a steady state and is not changing. The membrane potential part of the name comes from the fact that the electrical gradient created by active transport of ions across the cell membrane is a form of stored, or potential, energy, just as concentration gradients are a form of potential energy.

Physiological basis of resting membrane potential in a nerve fibre:

RESTING MEMBRANE POTENTIAL DEFINITION: The constant membrane potential present in all living cells when they are at rest (i.e. when they are not producing any electrical signals) is called their Resting membrane potential. All living cells show resting membrane potential which results from the uneven distribution of ions across the cell membranes. 2 Factors influence the Membrane Potential: Concentration gradients of various ions across the cell membrane. Membrane Permeability to those ions. Thus, it is the separation of charges that exists across a cell membrane separating the ICF and ECF in an excitable & non-excitable cell. The magnitude of the potential depends on the number of charges separated. The greater the number of charges separated, the larger the potential.

Question We know that the Resting Membrane Potential of human nerve cell membrane is —90 mv. What is the Physiological Basis of this RMP & how is it calculated??

Resting Membrane Potential in Neurons There is a great difference in the chemical composition of nerve cell interior(ICF) & exterior (ECF). ECF : ICF Na+:- 150 : 15 K+:- 5 : 150 The nerve cell interior (ICF) is rich in potassium ions (K) and negatively charged proteins while the ECF is rich in Sodium & Chloride ions. The unequal distribution of the key ions b/w the ICF & ECF and their selective movement through the plasma membrane are responsible for the electrical activity. Na is more concentrated in the extracellular fluid and K is more concentrated in the intracellular fluid. These concentration differences are maintained by the Na–K pump at the expense of energy. Because the plasma membrane is virtually impermeable to A, these large, negatively charged proteins are found only inside the cell. After they have been synthesized from amino acids transported into the cell, they remain trapped within the cell.

Various ions try to diffuse from one side of the membrane to the other depending upon their electrochemical gradients:

The Resting Membrane Potential is mostly due to Potassium Ions The neuron plasma membrane at rest is 100 times more permeable to K ions than to the Na ions!!!! This is through the help of the Potassium leak channels....

So, Now: Electrical gradient Chemical gradient for K+ for K+ This is the membrane potential at which the electrical gradient exactly opposes the concentration or chemical gradient and it is called the Equilibrium potential or the Nernst Potential for Potassium. Using the Nernst equation, when the Nernst potential for Potassium is calculated, it is -94 mv.

NERNST EQUILIBRIUM/ EUILIBRIUM POTENTIAL “The membrane potential at which the electrical gradient exactly opposes the concentration or chemical gradient is called the Equilibrium potential.” It is calculated by the Nernst equation. At this potential, the net movement of that particular ion STOPS.

NERNST EQUATION The Nernst equation can be used to calculate Nernst potential for any univalent ion at normal body temperature: EMF = ±61 log Conc. Inside Conc. Outside

Nernst Potential for Different Ions Using the Nernst equation, the Nernst Potential for different ions can be calculated. Na: +66mv K: — 94mv Cl: — 90mv When we see the values for different ions, we observe that the value for Potassium ion is the closest….

CALCULATING THE RMP: The RMP can be calculated using one of the 2 equations: NERNST EQUATION GOLDMAN’S OR GOLDMANN-HODGKIN-KATZ EQUATION Point to Remember: The greater the permeability of the plasma membrane for a given ion, the greater is the tendency for that ion to drive the membrane potential toward the ion’s own equilibrium potential.

Calculating the RMP by the Nernst Potential: Potassium ions: Nernst Potential for K+= —94mv Sodium ions: A very small number of Sodium ions move to the inside of the nerve cell despite a low permeability of the membrane to the Sodium ions. This is because of the small no. of Sodium leak channels present. They make a contribution of a small amount of electro positivity to the cell interior. Its value is= +8mv Sodium-Potassium Pump: expels 3 Na+ in exchange for 2 K+. It contributes= —4 mv So the total Resting Membrane Potential of a nerve cell is: RMP= —94 +8 —4 (mv) = —90 mv

Calculating the RMP by the GOLDMAN-HODGKIN-KATZ equation: Has 3 advantages: It keeps in mind the concentration gradients of each of the ions contributing to the RMP. It keeps in mind the membrane permeability of all the ions contributing to the RMP It can thus be used to calculate the RMP when multiple ions are involved rather than when only single ions are involved. Equation EMF= 61.log CNa i.PNa + Cki. Pk + CcloPcl CNao.PNa + Cko.Pk + CcliPcl = —90 mv If the membrane is not permeable to an ion, the permeability value for that ion is zero and the ion drops out of the equation. For example, cells at rest are not permeable to Calcium and so Calcium is not a part of the GHK.

What is the Physiological basis of the Resting Membrane Potential? PHYSIOLOGICAL BASIS OF THE RMP: -Calculation through the Nernst Equation and Goldman-Hodgkin-Katz equaation (Mushtaq: chapter: 2, NEURONS & SYNAPSES, page: 102-108, 5th edition). - Calculation through the Goldman-Hodgkin-Katz equation (Guyton: chapter 5, page: 59-60, 12th edition)

RMP POINT TO NOTE: Resting Membrane Potential is DETERMINED by the POTASSIUM IONS and has a value of ‒90 mv.

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