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: CONCENTRATION GRADIENT: 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 1. The membrane is electrically NEUTRAL! 2. The membrane carries NO charge! 3. The membrane is SELECTIVELY permeable. SEMIPERMEABLE MEMBRANE 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: 1. 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 - ECF: ICF: ECF: 3+, 5- ICF: 5+, 5- 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: 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. 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 Na+:K+:- 142 4 : ICF : : 14 140 The nerve cell interior (ICF) is rich in potassium ions (K) and negatively charged proteins while the ECF is rich in Sodium & Chloride ions. 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 for K+ Chemical gradient 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: 1. NERNST EQUATION 2. 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: 1. It keeps in mind the concentration gradients of each of the ions contributing to the RMP. 2. It keeps in mind the membrane permeability of all the ions contributing to the RMP 3. It can thus be used to calculate the RMP when multiple ions are involved rather than when only single ions are involved. 4. 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.