RESTING MEMBRANE POTENTIAL By Dr. Ayisha Qureshi Assistant Professor, Physiology MBBS, MPhil

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 and give the physiological basis of Resting membrane potential Use the Goldmann-Hoghkin-Katz equation to calculate the RMP Explain the contribution of Sodium-Potassium Pump to the RMP

REMEMBER: Like charges repel and unlike charge attract…..

CONCENTRATION GRADIENT: In the first picture, the membrane is IMPERMEABLE shown by the solid line. While in the second picture, the membrane becomes PERMEABLE & so the molecules are able to transfer to the other side.....

REMEMBER: A concentration gradient can exist for molecules/ particles and ions. Thus, a CHEMICAL gradient can exist in the presence of an ELECTRICAL gradient.

LIPID BILAYER The membrane is electrically NEUTRAL! The membrane carries NO charge! The membrane is SELECTIVELY permeable.

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 Role of Ion Channels

The role of Ion 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 – Channels which are opened through ligand binding (the ligand can be a hormone or a neurotransmitters or some other chemical.) Voltage Gated Channels – Channels which are opened by changes in the membrane potential

Nernst equilibrium/ Equilibrium potential:

ECF: Less +, more - ICF: more +, less - This diagram shows that there are more + inside the cell as compared to the ECF. Thus, there is a concentration gradient for + ions to move from the ICF to the ECF shown by the yellow arrow.

ECF: ICF: This diagram shows that the cell now has semi-permeable membrane, that allows the + ions to move to the ECF along their conc. Gradient but the same membrane does not allow the – ions to cross through. The + ions now pass through…. As they move along their concentration gradient, there is a net gain of + ions in the ECF but a net loss of + ions in the ICF. This leads to electronegativity on the inside of the plasma membrane of the cell. This electronegativity pulls back at the + ions as well. Thus, the + ions keep moving out along their chemical gradient and some of them keep getting pulled back into the cell because of the electric gradient (shown in red arrrow).

ECF: 3+, 5- ICF: 5+, 5- There will come a time when the outward pull of the + ion along its concentration gradient will exactly equal its inward movement along its electrical gradient. At this point, all net movement of that ion will STOP…. This is called the Equilibrium Potential for that ion (green arrow).

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

Physiological basis of resting membrane potential in a nerve fibre:

Figure a: The membrane is electrically neutral, with an equal number of positive & negative charges on each side of the membrane, no membrane potential exists. Figure b: Some of the + charges move from the right to the left side. Now the left side has an increase of + charges while the right side has more negative charges. Now there is a separation of charges across the plasma membrane and the opposite charges accumulate along the plasma membrane as they are attracted to the opposite charge. Figure c: The electrically balanced ions can be ignored because they do not contribute to the membrane potential. It is only a very small, almost insignificant number of ions that contribute to the membrane potential.

The separation of charges across the membrane. MEMBRANE POTENTIAL DEFINITION: The separation of charges across the membrane. OR The difference in the relative number of cations & anions in the ICF & ECF.

RESTING MEMBRANE POTENTIAL DEFINITION: The constant membrane potential present in the cells of excitable & non-excitable tissues when they are at rest (i.e. when they are not producing any electrical signals) is called their Resting membrane potential. 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.

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+:- 142 : 14 K+:- 4 : 140 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. In the body, the electrical charges are carried by the ions.

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

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.

CALCULATING THE RMP: The RMP can be calculated using one of the 2 equations: NERNST EQUATION GOLDMAN’S OR GOLDMANN-HODGKIN-KATZ EQUATION

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. EMF= 61.log CNa i.PNa + Cki. Pk + CcloPcl CNao.Pna + Cko.Pk + CcliPcl = —90 mv

PHYSIOLOGICAL BASIS OF THE RMP: -Calculation through the Nernst Equation (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.