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University of Baghdad College of Medicine 2024-2025 Title: Introduction to the excitable tissue Grade:2 Module: NS Speaker:Dr. Hanan Luay Date:  University of Baghdad/ College of Medicine 20...

University of Baghdad College of Medicine 2024-2025 Title: Introduction to the excitable tissue Grade:2 Module: NS Speaker:Dr. Hanan Luay Date:  University of Baghdad/ College of Medicine 2022-2023 Objectives: Upon completion of this lecture ,the student will be able to: 1-Define excitable tissues. 2-Identify the ionic basis of the resting membrane potential. 3-Describe the importance of Na⁺-K ⁺ pump. University of Baghdad/ College of Medicine 2022-2023  What is irritability? University of Baghdad/ College of Medicine 2022-2023 An ability of all living tissues to respond to stimuli (either external or internal environment) What is excitability? An ability of specialized cells to respond to certain stimuli by producing electrical signals known as action potential at its membrane  University of Baghdad/ College of Medicine 2022-2023 Muscle and nerve are excitable tissues. They are excitable because they have electrical phenomenon and able to transmit electochemical impulses i.e. they are polarized. The neurons are excitable cells specialized for reception, integration and transmission of nerve impulses. University of Baghdad/ College of Medicine 2022-2023  University of Baghdad/ College of Medicine 2022-2023 A 9-year-old boy is brought to the family physician after his parents noticed that he had difficulty moving his arms and legs after a soccer game. About 10 minutes after leaving the field, the boy became so weak that he could not stand for about 30 minutes. Questioning revealed that he had complained of weakness after eating few bananas, and had frequent muscle spasms.  University of Baghdad/ College of Medicine 2022-2023 What are 2 basic properties of excitable cell membranes? 1. The membranes have an electrical excitability across it, and may transmit an impulse along the membrane 2. The membranes contain a variety of ion channels (pores) that may be opened or closed, allowing specific ions to flow across. University of Baghdad/ College of Medicine 2022-2023  University of Baghdad/ College of Medicine 2022-2023 The electrical phenomena of the nerve cells: The cathode ray oscilloscope can be calibrated in such a way that an upward deflection of the line indicates that the inside of the membrane has become less negative (or more positive) compared to the outside of the membrane. A downward deflection of the line, conversely, indicates that the inside of the cell has become more negative.  University of Baghdad/ College of Medicine 2022-2023 As long as the electrodes are outside the membrane, the recorded potential is zero, which is the potential of the extracellular fluid as the electrode passes inside, the voltage decreases , and a membrane potential is recorded. Which is called the resting membrane potential  Nernest University of Baghdad/ College of Medicine 2022-2023 equation Nernst potential (Equilibrium potential) The potential level across the membrane that will exactly prevent net diffusion of an ion Nernst equation determines this potential  University of Baghdad/ College of Medicine 2022-2023 Note: none of the four most significant ions (Na+, The equilibrium potential for K+ is around -90 mv. While for Na + is around +60 mv (i.e no net movement of ion Cl-, K+, and Ca2+) in cell physiology is at across the membrane) electrochemical equilibrium in the normal This difference means that when the inside of the cell is physiological state. Instead, they all have nonzero 60 mV higher than the extracellular environment, Na+ electrochemical gradients across the cell will be in electrochemical equilibrium membrane. Even though ions are not at electrochemical equilibrium, the cell membrane And K+ will be in electrochemical equilibrium when the keeps their concentrations relatively stable. This cell is 90 mV lower than the extracellular environment. condition is referred to as a nonequilibrium steady - It is measured by Nernest equation state University of Baghdad/ College of Medicine 2022-2023  University of Baghdad/ College of Medicine 2022-2023 The leakage of K and Na ions through the nerve membrane It is because of the concentration gradient across the cell membrane, Na ions try to pass inside the cell down their concentration gradient.K ions try to pass outside the cell down the concentration gradient, but the channels in the cell membrane are more permeable to ions than to Na ions about 100 times.  Membrane potential: University of Baghdad/ College of Medicine 2022-2023 It means separation of electric charges across the membrane, or to a difference in the relative number of cations and anions in the intracellular fluid and extracellular fluid.  University of Baghdad/ College of Medicine 2022-2023 Resting membrane potential Membrane potential difference (transmembrane voltage) that exists when cell membranes of excitable tissues are not producing an action potential (at rest). The resting membrane potential of a large nerve fiber when not transmitting nerve signal is about -90 mv i.e. the potential inside the fiber is 90 mv (actually it is -70 mv in small nerve fibers, but -90 mv in large nerves).  University of Baghdad/ College of Medicine 2022-2023 The ionic basis of the resting membrane potential: 1-The contribution of the K⁺ion diffusion potential. 2-The contribution of the Na⁺ion diffusion potential through the nerve membrane. 3-The contribution of the Na⁺_K⁺ion pump. (contribute to 20% of the membrane potential)  University of Baghdad/ College of Medicine 2022-2023 Na- K pump University of Baghdad/ College of Medicine 2022-2023  University of Baghdad/ College of Medicine 2022-2023 The Na-K ion pump: It pumps Na ions to the outside of the cell and K ions to the inside, this pump requires energy. Because more positive charges are pumped to the outside than inside (3 Na ions to the outside for each 2 K ions to the inside) i.e. Na ions accumulate outside the cell while K accumulates inside the cell, ……………………………………… leaving a net deficit of positive ions inside leading to a negative potential across the membrane.  University of Baghdad/ College of Medicine 2022-2023 The final resting membrane potential reflects a balance between the electrochemical forces associated with each ion. The more permeable the membrane is for an ion, the more the equilibrium potential of that ion will influence the membrane potential.  University of Baghdad/ College of Medicine 2022-2023 In summary, -Muscle and nerve are excitable tissues and they are polarized. - They have resting membrane potential when there is no stimulus applied. -The 3 factors that contribute to the negative charges inside the membrane are: 1-The diffusion of k ions to the outside of the membrane is more than the diffusion of Na ions to the inside. 2-The Na-K pump. 3-The presence of negatively charged proteins inside the membrane.  University of Baghdad/ College of Medicine 2022-2023 Hyperkalemia  University of Baghdad/ College of Medicine 2022-2023 Another factor that can affect the overall membrane potential change is the overall resistance of the cell If many channels are open in a cell (i.e., the cell is "leaky"), the cell's input resistance will be low Under leaky conditions, it is difficult to change membrane potential Cl- channels often influence cell excitability by altering membrane resistance, rather than by directly altering membrane potential Barbiturates and Benzodiazepines act on a specific GABA(Neurotransmitter) receptor ; increasing the duration of Cl- channels opening, thereby increasing the influx of Cl- ions. As a The excitability of a nerve or muscle cell depends not only result, high intracellular concentrations of Cl- ions cause on the level of the membrane membrane hyperpolarization, which means it’s much more potential, but the overall difficult for the neuron to depolarize and fire off an action conductance of the cell (the input resistance). potential (decrease neuronal excitability).  University of Baghdad/ College of Medicine 2022-2023 In spite that in neurons, Cl− is a minor player in establishing the resting membrane potential (because the inside negative potential established by K+ serves as a force to limit the buildup of intracellular Cl−. Although Cl- is high extracellularly and moves intracellularly down its gradient). An increase in Cl− permeability is an effective way to “stabilize” the resting membrane potential by opposing changes in membrane potential that would be produced by fluxes of K+ or Na+. Conversely, a decrease in Cl− permeability make it easier for the membrane potential to shift away from its resting value. Thus, in the disease myotonia congenita (the inability of muscles to quickly relax after a voluntary contraction), the observed hyperexcitability of skeletal muscle cells is the result of a decrease in Cl− permeability (arising from defects in the Cl− channel) and thus decreases the stability of the resting membrane potential.  University of Baghdad/ College of Medicine 2022-2023 Clinical relevance *Hyperkaliemia may significantly interfere with the physiological functions of nerve cells or muscles. For example, it is known to induce dangerous arrhythmias.  University of Baghdad/ College of Medicine 2022-2023 *Cystic fibrosis (CF) is a disorder in which a transmembrane chloride transporter doesn’t function properly. In the respiratory airway, this leads to a lack of chloride movement from the inside of the cell to the outside of it. The more positive charge outside the cell leads to sodium ion movement into the cell. Water follows it, and this leaves the mucous in the respiratory tract dehydrated, sticky, and poorly functioning. This leads to frequent respiratory infections in patients with CF. University of Baghdad/ College of Medicine 2022-2023  University of Baghdad/ College of Medicine 2022-2023 So what is the difference between excitable and non excitable tissues? In non-excitable cells, such as epithelial cells and adipose cells, RBC (and others), the resting membrane potential does not change over time. In excitable cells, upon stimulation of the cell, the membrane potential can change dramatically for short periods of time (milliseconds).Therefore, in excitable cells the membrane potential is not always at the resting membrane potential.  University of Baghdad/ College of Medicine 2022-2023 In the central nervous system ion channels have been linked to many diseases such as ataxias, paralyses, epilepsies, and deafness Ion channel diseases are, in the narrower sense, mutations of the ion channels. e.g mutations in sodium channel genes , lead to a persistent sodium current and membrane hyper-excitability. In central neurons this results in epilepsy; in skeletal muscle it causes myotonia. Hemiplegic migraines and idiopathic ventricular fibrillation are also explained in this way On the other hand , loss-of-function mutations in potassium channel subunits prolong the action potential duration, inducing a hyper-excitability that can also lead to epilepsy, as well as cardiac disorders The sodium-potassium pumps can also be affected by diseases that affect the resting potential of a nerve cell. The modern western diet causes an unnatural sodium-potassium ratio in the body. The excess of table salt and a lack of potassium due to too little plant-based food can affect the sodium-potassium pumps, as this can change the intracellular ion ratio.  University of Baghdad/ College of Medicine 2022-2023 Circadian rhythm is the term used to describe a range of biological processes that change in a daily 24-h cycle. The neuronal firing frequency changes with a daily cycle and thus leads to cyclic changes in the melatonin secretion from the pineal gland. Melatonin, in turn, modulates a range of biological processes (such as sleep) One of the fundamental signals mediating the circadian firing cycles of some neurones (e.g SCN”‘suprachiasmatic nucleus” )is change in the RMP. Under control of the certain gene, some Ca2+-and K+ channel conductance are decreased in the afternoon, leading to a profound change of the RMP and a cessation of action potential firing in excitable cells  University of Baghdad/ College of Medicine 2022-2023 Reference: Guyton A.C. and Hall J.E (2006).Textbook of Medical Physiology.