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Objectives: 1) Review of Electrical Properties 2) The nervous system and the neurons 3) Electrical potentials of nerves 4) How neurons communicate? 5) How Human Nerve Cells Transmit Signals 6) Action potential, Refractory periods 7) Electrical signals from muscles electromyogram (EMG) 8) Electrical signals from the heart is called electrocardiogram (ECG) References: 1- Medical Physics textbook by Cameron 2- Physics in Biology and Medicine, Third Edition by Paul Davidovits 3- Physics of the Human Body, by Irving P. Herman We first review the various elements of electrostatics and current flow needed to understand electricity in the body, including the flow of an electrical pulse long an axon: The electric field at a distance r caused by a point charge q is given by Coulomb’s Law: E The constant k = 9 × 109 N-m2/ C2 The potential of that charge is: V kq r2 kq r In the body, charged ions, such as Na+, K+, Ca2+, Cl−, and negatively-charged proteins, are the important carriers of charge. Electrons are the charge carriers in most man-made electronic circuits. When a current flows along a material with resistance R (in ohms, Ω), there is a voltage drop V (in volts V) across the material given by Ohm’s law: V = IR a) Ohm’s Law and (b) evaluating resistance R from resistivity ρ The resistance is an extensive property that depends on the intensive property resistivity ρ of the material, and the cross-sectional area A and length L of the structure R L A A voltage or potential difference V can also develop between two structures, one with a charge +q and the other with charge −q, because of the electric fields that run from one to the other. This voltage is: V q C where C is the capacitance (in farads, F) of the system The capacitance C depends on the geometry of these two structures. For example, they could be two parallel plates or two concentric cylinders, which is similar to the axon of a neuron. Capacitance for (a) parallel plates and (b) cylindrical shells Neuron consists of the followings: 1- Dendrites: Short, branched & unmyelinated part of the neurons specialized for receiving electrical messages (signals) from stimuli or from other neurons towards the cell body. Its surfaces is specialized for contact with other neurons. 2- Soma (Cell body): Surrounded by cell membrane contains: nucleus & cytoplasmic organelles, it receives electrical messages (signals) from other neurons through body. [If the stimulus (such as touch, sound, light, and so on), is strong enough, the neuron will transmit an electrical signal outwards along a fiber called an axon]. 3- Axon (nerve fiber): Carries (propagates) and conveys electrical messages (signals) away from the cell body into the nerve terminals. Axons are ≈ 1 (m) long. There are two types of nerve fibers (myelinated and unmyelinated nerve fibers). 4- Axon terminals: Transmit electrical messages (information) from the neuron to muscles, glands or other neurons. Synaptic end bulbs: contain vesicles filled with neurotransmitters. The human brain is composed of billions of nerve cells which communicate through specialized connections called synapses (located on the dendrites or on the cell body). At each synapse, a chemical neurotransmitter is released from one cell and binds to receptors on the second cell. This chemical transmission generates electrical and biochemical signals in the second cell that are then passed along to a network of nerve cells. Thus, a synapse is the basic unit of communication in the brain. Building the correct network of synapses is essential for brain development and understanding how those synapses go is key to many neurological disorders. Neurotransmitters molecules are the red round dots which are released from the synaptic vesicles in the above cell to bind with the receptors sites in the cell bellow in order to generate electrical and biochemical signals in the second cell that are then passed along to a network of nerve cells. Dendrites Axon Synapse Nucleus The Axon maintains a chemical balance with more potassium (K+) ions inside the cell and sodium (Na+) ions outside the cell. Na Membrane of human +(Outside) nerve cell K+ (Inside) Na+ Dendrites Synapse Axon Na+ Na+ K+ K+ When signal is transmitted the myelin sheath changes so that the sodium (Na+) and potassium ions change places (sodium goes inside and potassium (K+) comes outside the myelin sheath). This results in an electrical change in the cell and this in turn causes the next section of myelin to change. Na+ Dendrites Synapse Axon K+ K+ K+ Electrical potentials of nerves: Across the surface or membrane of every neuron is an electrical potential (voltage) difference due to the presence of more negative ions on the inside of the membrane than on the outside. Neuron is said to be polarized (i.e. there is a slight potential difference between the inside of the cell membrane and the outside). The inside of the cell is more negative than the outside. This potential difference is called resting potential of the neuron. When neuron is stimulated, the resting potential changes to become positive inside the membrane with respect to outside at the point of stimulation. This potential change is called the action potential (AP) . Figure of action potential. (a) The action potential begins with the axon membrane becoming highly permeable to sodium ions which enter the axon making it positive. (b) The sodium gates then close and potassium ions leave the axon making the interior negative again. (a) (b) Action potential is defined as” a very rapid change in membrane potential that occurs when a nerve cell membrane is stimulated. Action potentials can travel up to100 meters/second. Specifically, the membrane potential goes from the resting potential to some positive value in a very short period of time (just a few milliseconds). AP is the major method of transmission of signals within the body which propagates along nerve axon. Components of action potential (AP) are: depolarization (reverse potential) and repolarization phases. ‘Movement' of action potentials is called an impulse. A nerve impulse is produced only if the stimulus exceeds a certain threshold value (threshold stimulus). When this value is exceeded, an impulse is generated at the point of stimulation and propagates down the axon. Such a propagating impulse is called an action potential. Potenti al (msec ) Action potentials occur only when the membrane in stimulated (depolarized) enough so that sodium channels open completely. The minimum stimulus needed to achieve an action potential is called the threshold stimulus. A nerve impulse is produced only if the stimulus exceeds a certain threshold value. When this value is exceeded, an impulse is generated at the point of stimulation and propagates down the axon. Such a propagating impulse is called an action potential. An action potential as a function of time at one point on the axon as shown in figure. There are SODIUM GATES and POTASSIUM GATES. These gates represent the only way that these ions can diffuse through a nerve cell membrane. There are lots of positively charged potassium ions just inside the membrane and lots of positively charged sodium ions PLUS some potassium ions on the outside. THIS MEANS THAT THERE ARE MORE POSITIVE CHARGES ON THE OUTSIDE THAN ON THE INSIDE. In other words, there is an unequal distribution of ions or a resting membrane potential. This potential will be maintained until the membrane is disturbed or stimulated. Then, if it's a sufficiently strong stimulus, an action potential will occur. Axon has a resting potential of about -70mV . If the left end of the axon is stimulated, the membrane walls become porous to Na+ and these ions pass through the membrane into the inside of the cell which, cause the membrane to depolarize. The depolarization process at the point of stimulation causes the next region to depolarize. Meanwhile, the point. of original stimulation has recovered (repolarized) because the out movement of K+ ions to restore the resting potential. Action potential of most neurons and muscle cells lasts a few milliseconds (msec = 10-3 sec) while for cardiac (heart ) muscle action potential may last from 150-300 (msec). Axon can transmit in either direction. However, synapse that connects it to another neuron only permits the action potential to move along the axon away from its own cell body. Membrane of some axons are covered with a fatty insulating layer called Myelin that has small un- insulated (un-myelinated, constricted) gaps called Nodes of Ranvier every few millimeters these nerves are referred to as myelinated nerves which conduct actions potentials much faster than unmyelinated nerves. While, axons of other nerves which have no myelin sheath are called unmyelinated nerves. All-or-None Law : Action potentials occur maximally or not at all. In other words, there's no such thing as a partial or weak action potential. Either the threshold potential is reached and an action potential occurs, or it isn't reached and no action potential occurs. A propagating impulse is called an action potential. Action potential is a function of time at one point on the axon. Polarized L Depolari zed Repolari zed R Conduction Velocity: Impulses typically travel along neurons from left to right side at a speed of anywhere from 1 to 120 m/sec. This speed of conduction can be influenced by: 1- Diameter of a nerve fiber. 2- Presence or absence of myelin sheath. [Neurons with myelin conduct impulses much faster than those without myelin]. Myelin sheath is a very good insulator and the myelinated segment of an axon has very low electrical capacitance. The action potential decreases in amplitude as it travels through the myelinated segments. The reduced signal then act like a stimulus at the next node of Ranvier (constriction) to restore the action potential to its original size and shape. Two primary factors affect the speed of propagation of the action potential (AP) in nerve axon: (1) The resistance within the core of the membrane. (2) The capacitance across the membrane. Capacitance refers to the ability of plasma membrane to store or separate charges of opposite signs, measured in Farad. 1) Resistance across the axon’s membrane [internal resistance of an axon decrease as the diameter of the axon increases so an axon with a large diameter will have higher velocity of propagation than an axon with a small diameter]. 2) Myelinated axons have low electrical capacitance (charge stored) than unmyelinated axons and the action potential seems to jump across the nodes of Ranvier [Saltatory conduction]. A decrease in either factors will increase the propagation velocity of action potential. The advantage of myelinated nerves is that they produce high propagation velocities in axons of small diameter. Speed of action potential propagation and axon diameter As the diameter of axon increases, the speed of action potential propagation along the axon increases (hence there is a direct relation between axon diameter and speed of action potential propagation along the axon). (Internal resistance) [Hence, Ri α 1/a2] ri= (R/L) i (ρi = conductivity of internal fluid) If the conductivity of the fluid inside an axon is 1.6 x 107 (Ωm), length of the axon is 90 (cm) and the axon diameter is 5 x10-6 (m). Calculate the value of the internal resistance (Ri) Ri = ρi L/πa2 ρi = 1.6 x 107 (Ωm) Length (L) = 90 (cm) = 0.9 (m) , Diameter = 5 x10-6 (m), radius (a) = 2.5 x 10-6 (m) π = 22/7 = 3.142857 Ri =(1.6 x107 x 0.9)/[3.142857 x (2.5 x 10-6)2]=(1.44 x 107)/[19.642857 x 10-12 ] Ri = 0.0733 x 1019 (Ω) The record of the potentials from muscles during movement is called EMG. Resting potential across the membrane of a muscle fiber is similar to resting potential across a nerve fiber. Muscle action is initiated by an action potential that travels along an axon and is transmitted across motor end plates (carry nerve impulses from the CNS) into the muscle fibers, causing them to contract. EMG electrodes usually record the electrical activity from several fibers. (EMG) measures the electrical activity of muscles at rest and during contraction. Nerve conduction studies measure how well and how fast the nerves can send electrical signals. Nerves control the muscles in the body by electrical signals (impulses), and these impulses make the muscles react in specific ways. Nerve and muscle disorders cause the muscles to react in abnormal ways. Measuring the electrical activity in muscles and nerves can help find diseases that damage muscle tissue or nerves. EMG and nerve conduction studies are often done together to give more complete information. Conduction velocity for sensory nerves which carry sensation from outside & inside the body to the CNS can be measured by stimulating at one site and recording at several locations that are known distances from the point of stimulation. Conduction velocity = Distance of response traveled from one location to another Time interval between two locations EMG Apparatus Muscle Structure/EMG Latency Latency or latent period is defined as follows: The period (interval, delay) elapsed between the presentation of a stimulus and the obvious response such as the contraction of a muscle. And it is also, the apparent inactivity between the time the stimulus is applied and the moment a response occurs. For example, the latent period between stimulation and the onset of muscle contraction is about 0.01 s. Conduction velocity in motor Conduction velocity in sensory nerve nerve The electrocardiograph (ECG) is an instrument that records surface potentials associated with the electrical activity of the heart. The surface potentials are conducted to the instrument by metal contacts called electrodes which are fixed to various parts of the body. Usually the electrodes are attached to the four limbs and over the heart. Voltages are measured between two electrodes at a time. Rhythmical action of the heart is defined as“ The ability of the heart to beat regularly and initiate its own regular repetitive beats independent on nerve supply”. This rhythmical action is controlled by an electrical signal initiated by spontaneous stimulation of special muscle cells located in the right atrium. These muscle cells make up the sinoatrial (SA) nodes or Heart Pacemaker (Initiate cardiac impulses). Electrical signals from SA node initiates the depolarization of the nerves and muscles of both left and right atrium, causing the atria to contract and pump blood into the ventricles. Repolarization of the atria then follows. A single cycle of cardiac activity can be divided into two basic phases - diastole and systole. Diastole represents: the period of time when the ventricles are relaxed. Throughout most of this period, blood is passively flowing from the left atrium (LA) and right atrium (RA) into the left ventricle (LV) and right ventricle (RV), respectively. The blood flows through atrioventricular valves that separate the atria from the ventricles. The RA receives venous blood from the body through the superior vena cava (SVC) and inferior vena cava (IVC). The LA receives oxygenated blood from lungs through four pulmonary veins that enter the LA. At the end of diastole, both atria contract, which propels an additional amount of blood into the ventricles. Systole represents: the time during which the left and right ventricles contract and eject blood into the aorta and pulmonary artery, respectively. During systole, the aortic and pulmonic valves open to permit ejection into the aorta and pulmonary artery. The atrioventricular valves are closed during systole, therefore no blood is entering the ventricles; however, blood continues to enter the atria though the vena cavae and pulmonary veins. Electrical signal then passes into the atrioventricular (AV) node via His bundle and the Purkinje fibers to the ventricles which, initiates the depolarization of the right and left ventricles causing them to contract and force blood into the pulmonary and general circulation. The ventricle nerves and muscles then repolarize and the sequence begin again. ECG is defined as “ The recording of cardiac action potentials during the cardiac cycle” Nerves and muscles of the heart can be regarded as source of electricity enclosed in an electrical conductor (torso). The record of the heart’s potentials on the skin is called (ECG). Electrodes for obtaining ECG are located on the left arm (LA), right arm (RA) and left leg (LL). Measurement of potential between RA and LA is called Lead 1, that between RA and LL is called Lead 2 and that between LA and LL is called Lead 3. The 3 leads are called standard limb leads. ECG recording R A L A Sensing points LL The heart may be considered to lie at the centre of an equilateral triangle and the corners of the triangles are the effective sensing points - the right arm (RA), left arm (LA) and left leg (LL) electrodes. [Lead 1 + lead 2 + lead 3= standard limb leads] Diagram of the heart, with its principle chambers, valves, and vessels There are four major valves in the heart. 1- The right atrioventricular valve controls flow between the right atrium and right ventricle it is also called the tricuspid valve. 2- The pulmonary semilunar valve controls blood flow from the right ventricle to the left and right pulmonary arteries. 3- The left atrioventricular valve controls flow from the left atrium to the left ventricle. It has two flaps and is therefore also called the bicuspid valve. Another name for this valve is the mitral valve, because it looks like a miter. 4- The aortic semilunar valve controls flow from the left ventricle to the aorta. ECG Signals Isoelectric line Isoelectric line P- wave: depolarization (contraction) of the right and left atria QRS complex: depolarization of the right and left ventricular (ventricular depolarization). ST wave: ventricular repolarization (relaxation). PR: Time interval from atrial depolarization to ventricular depolarization. QT: duration of ventricular depolarization and repolarization. ST: interval from the end of ventricular depolarization to the beginning of ventricular repolarization