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Chapter 3 Bioelectromagnetism Bioelectromagnetism is sometimes equated with bioelectricity. It is refers to the electrical, magnetic or electromagnetic fields produced by living cells, tissues or organisms. Examples include the cell membrane potential and the electric currents that flow in nerves and muscles, as a result of action potentials. Biological cells use bioelectricity to store metabolic energy, to do work or trigger internal changes, and to signal one another. Bioelectromagnetism is the electric current produced by action potentials along with the magnetic fields they generate through the phenomenon of electromagnetism. Bioelectromagnetism is studied primarily through the techniques of electrophysiology. In the late eighteenth century, the Italian physician and physicist Luigi Galvani first recorded the phenomenon while dissecting a frog at a table where he had been conducting experiments with static electricity. Galvani coined the term animal electricity to describe the phenomenon, while contemporaries labeled it galvanism. Galvani and contemporaries regarded muscle activation as resulting from an electrical fluid or substance in the nerves. Bioelectromagnetism is an aspect of all living things, including all plants and animals. Some animals have acute bioelectric sensors, and others, such as migratory birds, are believed to navigate in part by orienting with respect to the Earth's magnetic field. Also, sharks are more sensitive to local interaction in electromagnetic fields than most humans. Other animals, such as the electric eel, are able to generate large electric fields outside their bodies. In the life sciences, biomedical engineering uses concepts of circuit theory, molecular biology, pharmacology, and bioelectricity. Bioelectromagnetism is associated with biorhythms and chronobiology. 37 Biofeedback is used in physiology and psychology to monitor rhythmic cycles of physical, mental, and emotional characteristics and as a technique for teaching the control of bioelectric functions. Bioelectromagnetism involves the interaction of ions. Their are multiple categories of Bioelectromagnetism such as brainwaves, myoelectricity (e.g., heart-muscle phenomena), and other related subdivisions of the same general bioelectromagnetic phenomena. One such phenomenon is a brainwave, which neurophysiology studies, where bioelectromagnetic fluctuations of voltage between parts of the cerebral cortex are detectable with an electroencephalograph. This is primarily studied in the brain by way of electroencephalograms. 3.1 Bioelectricity of Cell Membranes Bioelectricity deals with cell membrane transport processes that control the formation and dissipation of ion gradients. Ion gradients store energy in form of an electrochemical potential. This energy can be converted into other forms of energy. The electrochemical potential is available to organisms for biosynthesis (photosynthesis and respiration), transport of metabolites (absorption and secretion), mechanical work (bacterial flagella rotor, swimming, crawling), and signaling processes (action potentials). Action potentials are a form of information used by electrically excitable membranes to control the activity of cells (calcium signaling, muscle contractility) and to support or suppress communication between cells (release of chemical signaling molecules; hormones, neurotransmitters). 3.2 Cell Membrane Cell membrane is a thin membrane that bound all living cells. It composed primarily of phospholipids and proteins and are typically described as phospholipids bi-layer as shown in figure 3.1. 38 Figure 3.1 The Cell membrane The spheres represent the phosphate, which is polar and water soluble (Hydrophilic). The twin extensions represent the fatty acid components which are not water soluble (hydrophobic). 39 Transport of Ions and Molecules through the Cell Membrane The membrane consist mainly of two parts: 1) Lipids Lipid bilayer : It is not miscible with either the extracellular fluid or the intracellular fluid. It constitutes a barrier for the movement of most water molecules and water-soluble substances. The type of diffusion here is Simple Diffusion. 2) Protein Channel Protein - - It have watery spaces all the way through the molecules and allow free movement of certain ions or molecules. - Highly selective in the types of molecules or ions that are allowed to cross the membrane. - The type of diffusion here is Simple Diffusion. Carrier Protein - It bind with substance that are to be transported, and conformational changes in the protein molecules 40 - It then move the substance trough the interstices of the molecule to the other side of the membrane. - The type of diffusion here is Facilitated Diffusion. Figure 3.2 Transportation through cell membrane Membrane permeability and the rate of diffusion The different factors that affect cell membrane permeability are: 1) Thickness of the membrane, the greater the thickness, the less the rate of diffusion. 2) Number of protein channels through which the substance can pass, the rate of diffusion is directly related to the number of channels per unit area. 3) The temperature, the greater the temperature, the greater is the thermal motion of molecules and ions in a solution. So the diffusion increases directly in proportion to temperature. 41 4) The molecular weight of the diffusing substance, the velocity of thermal motion of dissolved substance is inversely proportional to the square root of its molecular weight. 5) Area of the membrane, the permeability is directly proportional to the area of the membrane. Where dn/dt is the rate of diffusion, A is the area, d is the thickness and (C1 - C2) is the difference in concentration. Where D is the diffusion constant. d Where is the permeability of specific ion. 42 While if we write Thus dn/dt here is the rate of diffusion per unit area. dn/dt Simple Diffusion Facilitated C% Figure 3.3 The relation between diffusion rate and concentration 3.3 The Origin of Membrane Potentials 3.3.1 The Rest Potential It is important to understand the origin of membrane potentials. Biological membranes are electrical insulators due to their phospholipid bilayer structure and are impermeable to ions, unless specific ion channels are temporarily open. In real cells, several different ion types, each with its own gradient contribute to this charge separation. Any ion 43 that forms an ion gradient across a membrane, and that is permeable contributes to the actual membrane potential. At rest, most cells have a potential around -40 to -90mV indicating that they are dominated by K or Cl permeability (see table). Ion Intracellular Extracellular Na+ 10 mM + K 140 mM Cl5 mM Nernst Equation 100 mM 4 mM 125mM Ratio In : Out Nernst Potential 1 : 10 35 : 1 1 :25 + 60 mV 90 mV 70 mV V If we have two liquids differ in concentration where C1 ≠ C2 Thus there will be potential (Vc ) due to this difference where: C1 C2 If C2 = C1 Thus log 1 = 0 C1 ≠ C2 Figure 3.4 Potential due to difference in concentration Therefore Vc = zero For living cell C2 is concentration outside and C1 is concentration inside This means also it is for only one type of ions 44 Thus according to Nernst the total voltage = 90 + 60 – 70 = 100 mV However, the measured value is different this is due to Nernst considers that the permeability to all ions is equal and that is not true. Goldman’s Equation He solves the mistake of Nernst by considering the permeability of ions is relative permeability. Notice that for Cl- ions we use up the inside concentration and down the outside concentration this is due to the Cl is –ve so the field and potential is opposite to the other ions. Electrical equivalent circuit of membrane during rest state The concentration act as batteries connected in series to a resistor its magnitude is inversely related to the conductance of the membrane to the ion. Resistance of membrane to Na+ g Na = 1 VNa+ Resistance of +60 mV + membrane to K 45 VK + g = 100 k Resistance of -90 mV membrane to Cl- g Cl = VCl60 to 150 -70 mV RMP -70 mV Figure 3.4 The equivalent circuit of potential membrane The large resistance represents the low permeability of the membrane to Na+. While the small resistance represents the high permeability of the membrane to K+ and Cl-. RMP results from connecting the 3 batteries resistance combination in parallel. The membrane act as capacitor charges by RMP – 70 mV battery and resistance R of membrane. Outside RMP 46 Rm Inside Figure 3.5 The equivalent circuit of cell membrane 3.3.2 The Sodium-Potasium Pump The process of moving sodium and potassium ions across the cell membrane is an active transport process involving the hydrolysis of Adenosine triphosphate (ATP) to provide the necessary energy. It involves an enzyme refered to as: Where ADP is Adenosine diphosphate. This process is responsible for maintaining the large excess of Na+ outside the cell and large excess of K+ ions on the inside. Figure 3.6 (a - f) shows step by step how this process happen. Step 1 K+ K+ Three Na+ ions come close to the gate from 47 inside and two K+ ions Na+ Na+ Na+ Figure 3.6-a Step 1 Step 2 K+ K+ The Na+ ions enter the gate and the ATP come close Na+ Na+ Na+ P K+ K+ + Na + Na Na + P K+ K+ + Na + Na Na + P Figure 3.6-b Step 2 K+ Step 3 K+ The ATP stuck to the gate 48 Na+ Na+ Na+ P K+ K+ + Na + Na Na + P K+ K+ P + Na + Na Na + K+ K+ + Na + Na Na + Figure 3.6-c Step 3 Step 4 K+ K+ One Phosphate remain stuck to the gate and the ADP leave. The gate close from inside and open from outside. Na+ Na+ Na+ P K+ K+ + Na + Na Na + P K+ K+ + Na + Na Na + P K+ K+ + Na + Na Na + Figure 3.6-d Step 4 Na+ Na+ Na+ 49 Step 5 K+ K+ The Na+ ions leave the gate and go to the outside and two K+ ions enters the gate Figure 3.6-e Step 5 Na+ Step 6 Na+ Na+ K+ K+ P The Phosphate leave and the gate open from inside Then potassium ions enter the inside of cell K+ K+ + Na + Na Na + Figure 3.6-f Step 6 and close from outside. Stimulation We can classify stimulus into four types: 1Electrical 50 2Mechanical 3Thermal 4Chemical Any stimulus have intensity (height) and duration. Intensity Duration The Threshold value is the value in which below it no action potential happens. • If the initial depolarization is equal or more than it: 1- Membrane permeability to Na+ increases. 2- Positive feedback process happens. 3- Reversal of action potential from -70mV +20 mV. 3.3.3 The Action Potential Cell membranes have stable potentials (resting potentials) that depend on the gradients of permeable ions and in excitable cells can be induced to form self-propagating, dynamic action potentials. An action potential can be induced when the membrane potential changes electrotonically reaching a threshold needed to trigger an action potential as shown in Figure (3.7). The process involves several steps (for example for nerve cell): 1- A stimulus is received by the dendrites of a nerve cell. This causes the Na+ channels to open. If the opening is sufficient to drive the interior potential from -70mV up to -55mV. 51 2- Having reached the action threshold, more Na+ channels (sometimes called voltage-gated channels) open. The Na+ influx drives the interior of the cell membrain up to +30mV. The process to this point is called depolarization. 3- The Na+ channels close and the K+ channels open. Since the K+ channels are much slower to open, the depolarization has time to be completed. Having both Na+ and K+ channels open at same time would drive the system toward neutrality and prevent the creation of the action potential. 2 + 30mV 3 0 4 Depolarization Repolarization 55mV Gate Thershold Stimulus 6 70mV Rest Potential 1 90mV Hyperpolarizatio 5n Figure 3.7 The action potential curve 52 4- With the K+ channels open, the membrane begins to repolarize back toward to rest potential. 5- The repolarization typically overshoots the rest potential to about -90mV. This is called hyperpolatization. The hyperpolarization prevents the neuron from receiving another stimulus during this time, or at least raises the threshold foe any new stimulus. 6- After hyperpolarization, the Na+/K+ pump eventually brings the membrane back to its resting state of -70mV. 3.3 Membrane Currents Measuring membrane currents instead of potentials has been the way of understanding mechanisms underlying action potentials. Membrane currents are the result of opening ion selective channels which causes ions to flow across cell membranes. This flow is spontaneous because all ion types are distributed unevenly between cellular and extracellular compartments. In general, cell contain high loads of K+, but low Na+ and Ca++ ions, while extracellular fluids contain high Na+ and Ca++ ions, but low K+ concentrations. Accordingly, ion gradients ranging from 10 to 10,000 fold depending on the ion species exist. When channels are activated, ions will always start diffusing through the pores in either direction, although more ions will flow from the high to the low concentration (down hill). These ion diffusion is an important part of bioelectricity maintaining resting potentials and generating action potentials. It is also used to couple the transport of secondary solutes that can be up concentrated inside or outside according to metabolic needs. Finally, ATP hydrolyzing pumps reverse the flow of ions regenerating the gradients dissipated by the activity of channels and secondary transporters. Summarily, chemical energy is used to maintain the formation and use of membrane potentials and ion gradients. While almost all transporters somehow involve the flux of ions across membranes, ion channels are unique in their fast kinetics 53 facilitating the flow of up to 10 million ions per second. Pumps work at a roughly 10,000 fold slower rate. The methods to study membrane currents are voltage clamp (two electrodes) and patch clamp (one electrode) techniques. The latter allows the measurement of currents through single channel units, while the former is used to measure macroscopic currents, which are the result of the simultaneous activity of hundreds to thousands of channels. The noise recorded in the early days of electrophysiology indicated the presence of unit conductances which later have been correlated with the presence of ion channels, the physical units of electrical conductivity in cell membranes. 3.3.1 Electrocardiography Electrocardiography is a quick, simple, painless procedure in which the heart's electrical impulses are amplified and recorded on a piece of paper. This record, the electrocardiogram (ECG), provides information about the part of the heart that triggers each heartbeat (the pacemaker), the nerve conduction pathways of the heart, and the rate and rhythm of the heart. Usually, an ECG is obtained if a heart disorder is suspected. It is also obtained as part of a routine physical examination for most middle-aged and older people, even if they have no evidence of a heart disorder. It can be used as a basis of comparison with later ECGs if a heart disorder develops. 54 Figure 3.8 The electrocardiogram An electrocardiogram (ECG) represents the electrical current moving through the heart during a heartbeat. The current's movement is divided into parts, and each part is given an alphabetic designation in the ECG. Each heartbeat begins with an impulse from the heart's pacemaker (sinus or sinoatrial node). This impulse activates the upper chambers of the heart (atria). The P wave represents activation of the atria. Next, the electrical current flows down to the lower chambers of the heart (ventricles). The QRS complex represents activation of the ventricles. The electrical current then spreads back over the ventricles in the opposite direction. This activity is called the recovery wave, which is represented by the T wave. Many kinds of abnormalities can often be seen on an ECG. They include a previous heart attack (myocardial infarction), an abnormal heart rhythm (arrhythmia), an inadequate supply of blood and oxygen to the heart (ischemia), and excessive thickening (hypertrophy) of the heart's muscular walls. Certain abnormalities on ECG can also suggest bulges (aneurysms) that develop in weak areas of the heart's walls. Aneurysms may result from a heart attack. If the rhythm is abnormal (too fast, too slow, or irregular), the ECG may also indicate where in the heart the abnormal 55 rhythm starts. Such information helps doctors begin to determine the cause. To obtain an ECG, an examiner places electrodes (small round sensors that stick to the skin) on the person's arms, legs, and chest. These electrodes measure the magnitude and direction of electrical currents in the heart during each heartbeat. The electrodes are connected by wires to a machine, which produces a record (tracing) for each electrode. Each tracing shows the electrical activity of the heart from different angles. The tracings constitute the ECG. ECG takes about 3 minutes, is painless, and has no risks. 56