Resting Membrane Potential & Action Potential PDF

Faculty of Medicine Academic Year: 2024-2025 Year: 1 Semester: 1 Module: Human Body Function (HBF) 102  Resting Membrane Potential By: Dr. Mohamed abo el hassan Dr. Ramadan Saad Department: Physiology 11/26/2024...

Faculty of Medicine Academic Year: 2024-2025 Year: 1 Semester: 1 Module: Human Body Function (HBF) 102  Resting Membrane Potential By: Dr. Mohamed abo el hassan Dr. Ramadan Saad Department: Physiology 11/26/2024 2  OBJECTIVES 1. Define and list different membrane potentials. 2. Recognize the driving force(s) behind the development of RMP. 3. Relate equilibrium potential of an ion to the RMP of the cell membrane. 4- Identify “Nernst equation” application in neurophysiolog  Cell Membrane The cell membrane acts as a selective filter, allowing the free movement of some molecules across it while tightly controlling the movement of others. Movement of uncharged substances, like O2, CO2, urea, alcohol and glucose, depends only on their concentration gradient. The cell membrane is permeable to these molecules, and so they can move freely as their concentration gradients allow. Charged substances such as K+, Na+, Cl– ions, cannot easily diffuse through the cell membrane due to its internal hydrophobic structure. Hence, to cross the cell membrane charged substances will utilize ion channels (channels are selective for a particular ion or ions).  The Gibbs-Donnan effect "The Donnan Effect is the phenomenon of predictable and unequal distribution of permeant charged ions on either side of a semipermeable membrane, in the presence of impermeable charged ions“ This effect influences the ionic distribution across cell membranes, which is critical in maintaining the cell’s resting membrane potential.  Ion Concentration The large anion proteins in are not permeable to cell membrane. Because small cation [+] are attracted, but are not bound to the proteins, small anions will cross capillary walls away from the anionic proteins more readily than small cations.  The Donnan Effect on Ionic Distribution in Cells Cells contain impermeant anions, such as proteins and nucleic acids, which are negatively charged and unable to cross the cell membrane. This creates: A tendency for positively charged ions (like K⁺) to enter the cell to balance the negative charges. However, if too many ions move across, it would disrupt osmotic balance and potentially cause water to enter the cell, leading to swelling.  The Donnan Effect on Ionic Distribution in Cells Ion balance does equilibriate at the proportions that would be predicted by the Gibbs–Donnan model, because the cell cannot tolerate the attendant large influx of water. This is balanced by instating a functionally impermeant cation, Na+, extracellularly to counter the anionic protein. Small Na+ does cross the membrane via leak channels (the permeability is approximately 1/10 that of K+, the most permeant ion) but, as per the pump-leak model, it is extruded by the Na+/K+-pump. Ion Movement There are three factors that can induce the movement of the ions through ion channels: The concentration gradient: Ions would cross the membrane from a compartment with a higher concentration to the compartment with a lower concentration. The electrical gradient: Positive ions will be attracted to negative electrical potential and repelled from positive electric potential, and vice versa.  Interrelation of Donnan Effect and Resting Membrane Potential The Donnan effect influences the distribution of ions across the cell membrane, contributing to the ionic conditions that establish the resting membrane potential. Large anions (like intracellular proteins) that cannot cross the membrane contribute to the overall negative charge within the cell, which is essential for maintaining the resting membrane potential. In most resting neurons, the potential difference across the membrane is about 30 to 90 mV, with the inside of the cell more negative than the outside. That is, neurons have a resting membrane potential (or simply, resting potential) of about -30 to -90. Because there is a potential difference across the cell membrane, the membrane is said to be polarized. If the membrane potential becomes more positive than it is at the resting potential, the membrane is said to be depolarized. If the membrane potential becomes more negative than it is at the resting potential, the membrane is said to be hyperpolarized.  RESTING MEMBRANE POTENTIAL RMP: it is the potential difference across the cell membrane during rest, without stimulation between the inner side and the outer side, and it is relatively –ve inside. Normal Values : -70 in medium sized nerves and -90 mv in large nerve fibers. (inside the fiber is 90 times more negative) During rest, the membrane is polarized (the membrane is a wall between the positive outside and negative inside) There is high molecules of K+ inside the cell and high molecules of Na+ outside the cell. Excitable tissues of nerves and muscles cells have higher potentials than other cells (epithelial cells and connective tissue cells). Dead cells do not have membrane potentials.  Resting Membrane Potential + Cl- outside Na K+ + + + + + + + + + + + + + + + + + + + + + + Membrane - - - - - - - - - - - - - - - - - - - - - - inside - K + A Na+ Cl-  Basic physics of resting membrane potential 1- Contribution of K+ diffusion potential:- The cell membrane has tendency to pump potassium (K) (positive charge) out, from high to low, (outflux), causing –ve charge inside, through K leak channels, down its concentration gradient. (producing energy like Niagara falls, from high to low which gives energy to Canada) Result: Electro-positivity outside and electro-negativity inside. RMP is 100 times more permeable to K+ than Na+. (These K+ leak channels may also leak sodium ions slightly but are far more permeable to potassium than sodium) K diffusion contributes far more to resting membrane potential. (most important)  Basic physics of resting membrane potential 2- Contribution of Na diffusion through the nerve membrane: Very small amount of Na+ diffuses into the cell (from outside to inside) down its concentration gradient. The membrane is only slightly permeable to Na+ through K-Na leak channels. 3- Contribution of Na/K PUMP:- This is a powerful electrogenic pump on the cell membrane. maintains concentration gradients of K+ and Na+ between the two sides of the membrane. It pumps 3 Na+ to outside & 2 K+ to inside, causing a net loss of +Ve ions from inside, returning the nerve fibre to the resting state (-4 mV). Explain the role of the sodium-potassium (Na⁺/K⁺) pump in maintaining the resting membrane potential. How does it function, and what energy source does it use? What would happen to the resting membrane potential if the Na⁺/K⁺ pump were inhibited? Explain the process in detail. Q: What are the types of membrane ionic channels ? (1) Leak (Diffusion , Passive) channels : - Pores in the cell-membrane which are open all the time , therefore ions diffuse through them according to the ion Concentration Gradient. (2) Voltage-gated channels : open when the cell-membrane is electrically activated. (3) Chemically-gated ( ligand-gated ) channels : open by chemical neurotransmitters at neuromuscular junctions & synapses )connections b/w neurons).  The equilibrium Potential The electrical potential difference across the cell membrane that exactly balances the concentration gradient for an ion is known as the equilibrium potential. No net movement of ion in or out of the cell Nernst Equation The Nernst equation is used to calculate the value of the equilibrium potential of a particular cell for a particular ion: Ion species Nernst potential + K - 94 mV where Vm = equilibrium potential for any ion [V]; z = + Na + 61 mV valence of the ion, [C]0 = concentration of ion X outside of 2+ the cell [mol]; [C]i = concentration of ion X inside the cell Ca + 130 mV - [mol]. Cl - 80 mV  NERNST EQUATION -The Potassium Nernst (Equilibrium) Potential  At rest , K inside is 35 times higher than outside K+ leak channels → more K+ diffuses to outside than Na+ to inside , because K leak channels are far more permeable to K than Na about 50- 100 time due to small size of K molecules → more potassium lost than sodium gained → net loss of +ve ions from inside the cell → more negative inside (net K OUTFLUX TO OUTSIDE causing –ve inside)  Applying Nernst Equation:- -K inside is 35 times higher than outside (35/1) - Nernst potential = - 61 x log 35/1 (1.54) = -94 mV, (if K is the only ion act on membrane →RMP = -94 mv with negativity inside the nerve).  Simplest Case Scenario: inside outside If a membrane were permeable to only K+ then… K+ K+ The electrical potential that counters net diffusion of K+ is called the K+ equilibrium potential (EK). So, if the membrane were permeable only to K+, Vm would be -94 mV 22 The Sodium Nernst (Equilibrium) Potential Na leak channels:- have Slight permeability to Na ions from outside to inside. Nernst potential = + 61 x log ( Na inside/ Na outside = 0.1) = + 61 x log 0.1= + 61 mV -Nernst potential for Na inside membrane = + 61mV (if Na is the only ion acting on the membrane → RMP = + 61mV with positivity inside the nerve  Simplest Case Scenario: inside outside If a membrane were permeable to only Na+ then… Na+ would diffuse down its concentration Na+ Na+ gradient until potential across the membrane countered diffusion. The electrical potential that counters net diffusion of Na+ is called the Na+ equilibrium potential (ENa). So, if the membrane were permeable only to Na+, mV would be +61 mV 24  Why is Vm so close to EK? Ans. The membrane is far more permeable to K+ than Na+. Normal conditions EK -94 Vm -74 ENa+61 0 mV 20 mV 135 mV The resting membrane potential is closest to the What is the net driving force on K+ ions? equilibrium potential for What is the net driving force on Na+ ions? the ion with the highest Which way do the ions diffuse? permeability! What effect does increasing Na+ or K+ permeability (or extracellular concn) have on Vm? 25  Carry Home Message The Donnan effect creates an unequal distribution of permeable ions due to the presence of impermeant ions on one side of a membrane, leading to a potential difference. In cells, this effect contributes to the resting membrane potential and influences ionic distribution. Active transport (such as the Na⁺/K⁺ pump) is essential to sustain ionic gradients and prevent osmotic imbalance, maintaining cell stability and function. This balance of ionic gradients and membrane potential is fundamental for cell function, particularly in excitable cells like neurons and muscle cells. 11/26/2024 26 1. At rest, the cell membrane is most permeable to which ion? A. Sodium (Na⁺) B. Potassium (K⁺) C. Calcium (Ca²⁺) D. Chloride (Cl⁻) 2. A toxin that blocks potassium channels in a neuron would likely cause the resting membrane potential to: A. Depolarize (become more positive) B. Hyperpolarize (become more negative) C. Remain the same D. Oscillate 3. Which of the following ions has a positive equilibrium potential in a typical neuron? A. Sodium (Na⁺) B. Potassium (K⁺) C. Chloride (Cl⁻) D. None of the above 11/26/2024 28  Faculty of Medicine Academic Year: 2024-2025 Year: 1 Semester: 1 Module: Human Body Function (HBF) 102  ACTION POTENTIAL By: ASHRAF ALGENDY PROFESSOR Department: MEDICAL PHYSIOLOGY 11/25/2024 22  prerequisites Before the lecture you must know:  Different types of channelS in plasma membrane.  Definition and mechanism of resting membrane potential.  Different types of transport across the cell membrane. 11/25/2024 HBF - 102 4  OBJECTIVES At the end of the lecture you will be able to:  understand essential terminology related to different electrical activities of excitable tissues.  Define different electrical activities of excitable tissues.  Clarify the importance of action potential. 11/25/2024 HBF - 102 5  OBJECTIVES At the end of the lecture you will be able to:  List and discriminate different types of action potential.  Draw and labels different phases of monophasic action potential. 11/25/2024 HBF - 102 6  OBJECTIVES At the end of the lecture you will be able to:  Explain the mechanism of different phases of monophasic action potential.  Recognize excitability changes that coincided with monophasic action potential. 11/25/2024 HBF - 102 7  Introduction The process of communication between the nerves and their target tissues was a big unknown for physiologists. With the development of electricity, electrophysiology and the discovery of electrical activity of neurons, it was proved that the transmission of signals from neurons to their target tissues is mediated by action potentials.  OBJECTIVES At the end of the lecture you will be able to:  understand essential terminology related to different electrical activities of excitable tissues.  Define different electrical activities of excitable tissues.  Clarify the importance of action potential. 11/25/2024 HBF - 102 10  polarization It is potential difference between outer surface and inner surface of excitable tissue during rest Value in medium sized nerve = - 70 11/25/2024 Helwan Special Medical Program 11 11/25/2024 Helwan Special Medical Program 12 11/25/2024 Helwan Special Medical Program 13  depolarization It is raising membrane potential toward positive value, i.e. decrease negativity inside the cell Value = - 69 up to -1 11/25/2024 Helwan Special Medical Program 14 11/25/2024 Helwan Special Medical Program 15  Loss of polarity No potential difference between outer surface and inner surface of excitable tissue Value = zero 11/25/2024 Helwan Special Medical Program 16  Reverse of polarity The inner surface of the membrane is positive in relation to outer surface Value = up to +35 11/25/2024 Helwan Special Medical Program 17  Repolarization Return membrane potential to normal state Value = - 70 11/25/2024 Helwan Special Medical Program 18 11/25/2024 Helwan Special Medical Program 19  Hyperpolarization The inner surface of the membrane is more negative than resting state Value = - 80 or more 11/25/2024 Helwan Special Medical Program 20 11/25/2024 Helwan Special Medical Program 21  OBJECTIVES At the end of the lecture you will be able to:  understand essential terminology related to different electrical activities of excitable tissues.  Define different electrical activities of excitable tissues.  Clarify the importance of action potential. 11/25/2024 HBF - 102 23 Electrical activities of excitable tissue Resting membrane potential. Electrotonus. Action potential. Electrical activities of excitable tissue Electrotonus. Local electrical changes that occur in excitable tissue when stimulated by subthreshold stimuli. Electrical activities of excitable tissue Action potential Series of brief, self propagated electrical changes that occur in excitable tissues when stimulated by adequate stimuli. 11/25/2024 Helwan Special Medical Program 28 11/25/2024 Helwan Special Medical Program 29  OBJECTIVES At the end of the lecture you will be able to:  understand essential terminology related to different electrical activities of excitable tissues.  Define different electrical activities of excitable tissues.  Clarify the importance of action potential. 11/25/2024 HBF - 102 30 Clinical significance of action potential ❖ Nerve Impulse Transmission Action potentials are the basis of nerve impulse transmission, allowing for. communication between neurons and other cells. Clinical significance of action potential ❖ Excitation contraction coupling. ❖ Excitation secretion coupling. ❖ Medical diagnosis : ECG ,EEG 3 Medical and EM Diagnosis  Clinical significance of action potential ❖ Research in neuroscience and AI field. List clinical significance of action potential? 11/25/2024 Helwan Special Medical Program 35  OBJECTIVES At the end of the lecture you will be able to:  List and discriminate different types of action potential.  Draw and labels different phases of monophasic action potential. 11/25/2024 HBF - 102 36 Types of action potential Monophasic Biphasic compound Types of action potential Monophasic Electrical activities of excitable tissue Monophasic Action potential of medium sized nerve 11/25/2024 Helwan Special Medical Program 40 Electrical activities of excitable tissue Monophasic Action potential of large sized nerve and skeletal muscle 11/25/2024 Helwan Special Medical Program 42 Electrical activities of excitable tissue Monophasic Action potential of non-nodal ventricular cardiac muscle 11/25/2024 Helwan Special Medical Program 44 Electrical activities of excitable tissue Monophasic Action potential of nodal cardiac muscle 11/25/2024 Helwan Special Medical Program 46 Types of action potential Biphasic 11/25/2024 Helwan Special Medical Program 48 Types of action potential Monophasic Biphasic compound 11/25/2024 Helwan Special Medical Program 50 11/25/2024 Helwan Special Medical Program 51  OBJECTIVES At the end of the lecture you will be able to:  List and discriminate different types of action potential.  Draw and labels different phases of monophasic action potential. 11/25/2024 HBF - 102 52 11/25/2024 Helwan Special Medical Program 53 11/25/2024 Helwan Special Medical Program 54 11/25/2024 Helwan Special Medical Program 55  OBJECTIVES At the end of the lecture you will be able to:  Explain the mechanism of different phases of monophasic action potential.  Recognize excitability changes that coincided with monophasic action potential. 11/25/2024 HBF - 102 56 57 11/25/2024 Helwan Special Medical Program 58  Rapid depolarization Loss of Firing level polarity Slow Reverse of depolarization polarity Rapid RMP repolarization Hyper Slow polarization repolarization 59  Selective permeability Na/K pump 11/25/2024 Helwan Special Medical Program 61  Caused by subthreshold stimulus 11/25/2024 Helwan Special Medical Program 62 11/25/2024 Helwan Special Medical Program 63 What ion enters a neuron causing depolarization of the cell membrane? A) phosphate. B) chloride C ) sodium D) potassium. E) calcium. Depolarization Stimulus A stimulus triggers depolarization, making the inside of the neuron more positive. Sodium Channels Open Sodium channels open, allowing sodium sodium ions to rush into the cell. Membrane Potential Rises The influx of sodium ions causes the membrane membrane potential to become more positive positive  Voltage –Gated Sodium channel The activation gate opens when the Activation Gate membrane potential reaches a certain certain threshold. The inactivation gate closes shortly after the activation Inactivation Gate gate opens, limiting the flow flow of sodium ions.  Rapid depolarization Sodium Influx The rapid influx of sodium ions causes a steep rise in the membrane potential. Positive Feedback As the membrane potential rises, more sodium channels channels open, accelerating the depolarization process. process. Peak Potential The membrane potential reaches a peak value, typically typically around +30 mV. 11/25/2024 Helwan Special Medical Program 70 Repolarization 1 Sodium Channels Close Sodium channels inactivate, stopping the influx of influx of sodium ions. 2 Potassium Channels Open Potassium channels open, allowing potassium ions to flow out of the cell. 11/25/2024 Helwan Special Medical Program 74 Hyperpolarization 3 Membrane Potential Falls The efflux of potassium ions causes the membrane potential to become more negative. Repolarization Na/K PUMP causes the membrane potential returning towards its resting value (RMP). 11/25/2024 Helwan Special Medical Program 78  OBJECTIVES At the end of the lecture you will be able to:  Explain the mechanism of different phases of monophasic action potential.  Recognize excitability changes that coincided with monophasic action potential. 11/25/2024 HBF - 102 79  Response of the excitable tissues when stimulated by threshold stimuli 1 ELECTRICAL CHANGES (AP) 1. EXCITABILITY CHANGES 1.. THERMAL CHANGES 1… METABOLIC CHANGES EXCITABILITY CHANGES 1 Absolute Refractory Period (ARP) 2 Relative Refractory Period (RRP) 3 Super Normal Phase (SNP) 4 Sub-Normal Phase (Sub NP)  Excitability = zero ARP Excitability more than zero but less than RRP normal Excitability more than normal but less than SNP normal Excitability more than zero but less than Sub NP normal  No response what ever the strength of ARP stimuli Only suprathreshold stimuli can produce RRP response SNP Subthreshold stimuli can produce response Only suprathreshold stimuli can produce Sub NP response  Coincide with rapid depolarization and early ARP part of rapid repolarization Coincide with late part rapid of rapid RRP repolarization. SNP Coincide with after depolarization. Sub NP Coincide with after hyperpolarization. 11/25/2024 Helwan Special Medical Program 86 Summary 88 88  References ❖ Linda S. Costanzo: physiology, six edition, ELSEVER. ❖ Linda S. Costanzo: BRS physiology, seventh edition, Lippincott Williams & Wilkins. ❖ Lecture notes. 11/25/2024 HBF - 102 89 89