Membrane Potentials - 17-18 RMP 2 PDF

Wondershare PDFelement Membrane potentials Dr. Hader I. Sakr Associate professor, Medical Physiology  ‫‪Wondershare‬‬ ‫‪PDFelement‬‬ ‫ﺴﻢ ﷲ اﻟﺮﲪﻦ اﻟﺮﺣﲓ‬ ‫﴿ َواﺗ ُﻘﻮا ا َ ۖ َوﯾ ُ َﻌ ُ ُ َ ُ‬...

Wondershare PDFelement Membrane potentials Dr. Hader I. Sakr Associate professor, Medical Physiology  ‫‪Wondershare‬‬ ‫‪PDFelement‬‬ ‫ﺴﻢ ﷲ اﻟﺮﲪﻦ اﻟﺮﺣﲓ‬ ‫﴿ َواﺗ ُﻘﻮا ا َ ۖ َوﯾ ُ َﻌ ُ ُ َ ُ‬ ‫ا‬‫و‬ ‫ۗ‬ ‫ا‬ ‫ُ‬ ‫ﲂ‬ ‫ُ‬ ‫ﻤ‬‫ّ‬ ‫ِ‬ ‫ﻠ‬ ‫ﳾ ٍء َ ِﻠ ٌﲓ﴾‬ ‫ِ ُ ِّ‬ ‫ﲁ َْ‬  Wondershare PDFelement Learning objectives: Membrane potential. Different membrane potentials. How to measure membrane potentials. Ionic Basis of RMP. Strength-duration curve.  Wondershare PDFelement Membrane potential  Wondershare PDFelement Membrane potential  The cell membrane is responsible for the marked differences in the ionic composition of ICF and ECF.  Large amounts of K+, proteins, Mg+2 and PO4- accumulate inside the cell, while excess Na+, Cl- and HCO3- are found in the ECF.  As a result, an electrical potential [voltage] difference exists between the inside and outside the cell. This is called trans-membrane or membrane potential.  Membrane potential exists across the membranes of essentially all cells of the body.  Wondershare PDFelement Membrane potential  Membrane potential is responsible for a property in all living cells called excitability.  Excitability is the ability of living tissues to respond to changes in its environments whether internal or external (stimuli).  The most excitable tissues in the body are nerves and muscles.  Nerves can be stimulated by many different stimuli: 1. Electrical. 2. Mechanical. 3. Chemical. 4. Thermal.  Wondershare PDFelement Membrane potential  The electrical stimulus is preferred because: 1- It is similar to the natural stimuli inside the body. 2- It can be controlled. 3- It can be accurately measured. 4- It leaves the tissue undamaged.  It order to stimulate a nerve electrically, two stimulating electrodes are placed on its surface, one is connected to the +ve pole [anode] & the other to the -ve pole [cathode].  When the stimulator is turned on, current enters the nerve at the anode, moves along the interior of the fiber and leaves the nerve at the cathode.  Wondershare PDFelement Different membrane potentials  Wondershare PDFelement Different membrane potentials  Membrane potential in nerve has many forms: I- Under resting conditions: a resting (steady) membrane potential is recorded. II- On stimulation of the nerve by: a. Inadequate (subthreshold) stimulus: Localized (electrotonic or graded) potenetials are recorded. b. Adequate stimulus, an action potential is recorded. Wondershare PDFelement  Wondershare PDFelement Different membrane potentials  Resting Membrane Potential (RMP - Polarized State): - It is the difference in electrical potential (voltage) between the inside and outside membrane surfaces under resting “unstimulated“ conditions, with the inside negative relative to the outside. - This RMP is found in almost all cells (both excitable and non- excitable tissues), but more marked in nerve and muscle cells. - In large nerve and skeletal muscle fibers, RMP is about -90 mV, but in medium-sized neurons it is usually about -70 mV. - However, in non-excitable cell [e.g. RBCs & epithelial cells] R.M.P is approximately -20: - 40 mV.  Wondershare PDFelement How to measure membrane potentials  Wondershare PDFelement How to measure membrane potentials  For measuring membrane potential of a nerve fiber, 2 microelectrodes are used. One on the surface of the fiber membrane and the other is dipped inside the fiber.  Both electrodes are connected through an electronic amplifier to a voltmeter to measure the very small voltages.  Wondershare PDFelement Ionic Basis of RMP  Wondershare PDFelement Ionic Basis of RMP  Causes (Ionic Basis) of RMP.: - The RMP is due to unequal distribution of ions on both sides of the cell membrane. - In nerve and muscle, it is determined mainly by the selective membrane permeability for Na+ & K+ and by the Na+/K+ pump mechanism. 1 - Selective Permeability of Membrane: - The [K+] is very great inside the membrane and is very low outside. - At the same time, most of Na+ accumulates outside the nerve fiber. - Diffusion is the main factor which determines RMP. - Na+ influx according to their electrochemical gradients. - K+ efflux according to their concentration and against their electrical gradients.  Wondershare PDFelement Ionic Basis of RMP - The resting cell membrane is more permeable to K+ ions. For example, most mammalian cell membranes are 50 to 100 times more permeable to K+ than to Na+ or other ion species. - Thus, the amount of K+ outflow, through K+ leak channels (Tandem pore domain) is much greater than amount of Na+ inflow. - In addition, the membrane is impermeable to intracellular proteins & other organic anions (phosphate and sulfate compounds), which represent most of the intracellular anions.  Wondershare PDFelement Ionic Basis of RMP - The net effect is accumulation of positive ions on the outer surface and negative ions on the inside of the membrane. 2 - Sodium-Potassium Pump Mechanism: - More +ve charges are pumped to the outside than to the inside [3Na+ ↑ for each 2K+ ↓. - This leaves a net deficit of +ve ions on the inside (electrogenic) and helps to keep resting membrane potential.  Wondershare PDFelement Ionic Basis of RMP Relative Contributions of Ion Fluxes and Na+ - K+ Pump to RMP:  Wondershare PDFelement Ionic Basis of RMP Relative Contributions of Ion Fluxes and Na+ - K+ Pump to RMP:  Wondershare PDFelement Ionic Basis of RMP  Relative contributions of ion fluxes and Na+ - K+ Pump to RMP: - Each ion try to reach an equilibrium potential where the flow of ion in one direction is balanced by its flow in the opposite direction “i.e. equal rates of ion influx and efflux“. - At equilibrium, the ratios of these ions from the inside to the outside are: - The equilibrium potential for K+ is -94 mV and for Na+ is +61 mV as proved by Nernst equation (discussed later), thus at RMP (-90mV) there is continuous K+ efflux and Na+ influx in order to reach their equilibrium.  Wondershare PDFelement Ionic Basis of RMP [A] Contribution of the Potassium Diffusion Potential: - Nernst Equation which is used to calculate the equilibrium potential [Nernst potential] for any univalent ion at normal body temperature of 37c°. - The sign of the potential is positive (+) for anions and negative (-) for cations. - If we assume that the only movement of ions through the membrane is the diffusion of K +, then the membrane potential at the equilibrium stage will be the Ep for K+. - The predicted Ep for K+ as calculated from Nernst equation: = -94 mV. - This means that if K+ was the only factor causing the RMP, it would be equal to - 94 mV.  Wondershare PDFelement Ionic Basis of RMP [B] Contribution of the sodium diffusion potential: - The predicted equilibrium potential for Na+ as calculated from Nernst equation is: = +61 mV. - This means that if Na+ was the only factor causing the RMP, it would be equal to +61 mV. [C] Goldman-Hodgkin-Katz (GHK) Equation: - It calculates the membrane potential more accurately by involving Na+, K+ and Cl- altogether taking in consideration: a) The concentration of Na+, K+ and Cl- inside and outside the membrane. b) The relative permeability of membrane to each of these ions.  Wondershare PDFelement Ionic Basis of RMP - According to this equation the predicted R.M.P. by diffusion of ion is - 86 mV [about 95 % of RMP]. [D] Contribution of the Na+ - K+ pump: - The continuous loss of positive charges from inside the membrane creates an additional degree of negativity [about - 4 mV. Additional, i.e. about 5% of RMP] on the inside.  Wondershare PDFelement Strength-duration curve  Wondershare PDFelement Strength-duration curve Chronaxie Wondershare PDFelement Wondershare PDFelement Wondershare PDFelement  Wondershare PDFelement Strength-duration curve  There is an intimate relation between the strength of the stimulating current & the length of time it must be applied to the nerve to produce a response. a) Within limits: the stronger the stimulus, the shorter its duration needed to excite the nerve, i.e. to produce a nerve impulse. b) Stimuli of extremely short duration will not excite the nerve no matter how intense they may be. c) Rheobase [threshold stimulus]: is the minimum amount of current intensity necessary to produce nerve activity. d) Utilization time: the time needed for the rheobase stimulus to give a response e) Chronaxie: is the time needed by a double rheobase stimulus to produce a response.  Wondershare PDFelement Strength-duration curve N.B.: Stimuli having intensities below the threshold are called "subthreshold or subminimal stimuli. A subminimal stimulus is not without effect on the nerve. It causes localized changes in the nerve known as local response or local excitatory state.  Wondershare PDFelement Strength-duration curve  Factors affecting effectiveness of electric stimulus: 1. Strength (intensity) of the stimulus: An effective stimulus needs certain amplitude to excite the nerve and produce a nerve impulse. 2. Duration of the stimulus: An effective current must be applied for a certain period to give response. 3. Rate of rise of stimulus intensity: Rapidly increased stimulus intensity to threshold value will give active response. But, a slowly increased intensity will not give response as the nerve would accommodate to it [see nerve accommodation]. Wondershare PDFelement  Wondershare PDFelement Conclusion Membrane potential exists essentially in all living cells. Membrane potential has different states under resting and stimulating conditions. Membrane potential could be measured by voltmeter. RMP is caused by selective permeability [95%] and Na+/K+ pump activity [5%]. There is an inverse relation between the intensity & the duration of the stimulus. The strength, duration and rate of rise of the stimulus affect its effectiveness.  Wondershare PDFelement References Guyton and Hall, 13th edition. Unit II(5); 61-4. Ganong’s review of medical physiology 25th ed. Section I(4); 89-90.  Wondershare PDFelement Thank You