Physiology of Excitable Tissues PDF

PHYSIOLOGY OF EXCITABLE TISSUES LECTURER: Mr Allen  INTRODUCTION The four basic types of tissue found in the body are connective tissue, epithelial tissue, muscle tissue, and nervous tissue. All animal cells have a membrane potential, and speci...

PHYSIOLOGY OF EXCITABLE TISSUES LECTURER: Mr Allen  INTRODUCTION The four basic types of tissue found in the body are connective tissue, epithelial tissue, muscle tissue, and nervous tissue. All animal cells have a membrane potential, and specialized electrical properties have developed in many. Excitable tissues are those tissues capable of generation and transmission of electrochemical impulses along the membrane. There cell membranes have the capacity to generate rapidly changing electrochemical impulses. These impulses can be used to transmit signals along cell membranes. Nerves and muscles are capable of generating and propagating action potentials (APs). Excitation of these tissues may be electrical, chemical, or mechanical. The human body relies on the proper functioning of excitable tissues to facilitate vital physiological processes, including muscle contraction, nerve conduction, and cardiac activity  INTRODUCTION CONT’D Nerve tissues contain neurons that serve as carriers of electrical impulses over long distances. Muscle tissue generates mechanical force in response to electrical stimulation. For example, in heart cells, the electrical and permeability properties are specialized as timing devices to control the rate of the heartbeat. The contractile apparatus of muscle fibers is under electrical control, and is activated when the membrane potential exceeds a threshold value. In glandular tissues, secretion of transmitters, and possibly hormones, is triggered by membrane potential changes. In intestinal cells, the membrane potential aids in the uptake of glucose and amino acids. These tissues share common characteristics related to their excitability, AP generation, and conduction properties. The ability of excitable tissue to generate and propagate APs depends upon the electrical properties of the cell membrane at rest  BRIEF DESCRIPTION OF THE STRUCTURE OF EXCITABLE TISSUES:- MUSCLE TISSUES Human body has more than 600 muscles Muscle tissue is characterized by properties that allow movement. These properties are excitability and contractility Muscle cells are excitable; they respond to a stimulus. They are contractile, meaning they can shorten and generate a pulling force Muscles are classified by three different methods, based on different factors: I. Depending upon the presence or absence of striations II. Depending upon the control III. Depending upon the situation.  SKELETAL MUSCLE Skeletal muscle is situated in association with bones forming the skeletal system. The skeletal muscles form 40% to 50% of body mass and are voluntary and striated. These muscles are supplied by somatic nerves. The diameter of a typical skeletal muscle cell is about 100 µm. Fibers of the skeletal muscles are arranged in parallel. In most of the skeletal muscles, muscle fibers are attached to tendons on either end. Skeletal muscles are anchored to the bones by the tendons. The muscle cell, or myocyte, develops from myoblasts derived from the mesoderm. Myocytes and their numbers remain relatively constant throughout life. Skeletal muscle tissue is arranged in bundles surrounded by connective tissue. Under the light microscope, muscle cells appear striated with many nuclei squeezed along the membranes. The striation is due to the regular alternation of the contractile proteins actin and myosin, along with the structural proteins that couple the contractile proteins to connective tissues. The cells are multinucleated as a result of the fusion of the many myoblasts that fuse to form each long muscle fiber. The plasma membrane of skeletal muscle cells (the sarcolemma) is specialized in that it has invaginations that run deep into the muscle cell. These invaginations are referred to as transverse tubules (or tubules). It is important to say that the membrane of the t-tubule is continuous with the sarcolemma. The t-tubules serve to allow muscle action potentials to reach deep into the muscle cell. It is also important to recognize that the lumen of the t-tubule is the extracellular fluid. Within the cytoplasm of the skeletal muscle fiber (myoplasm or sarcoplasm), there are numerous specialized structure. A highly specialized endoplasmic reticulum referred to as the sarcoplasmic reticulum is tightly wrapped around individual myofibrils and functions to store a high concentration of Ca2+. The release of Ca2+ from the sarcoplasmic reticulum is responsible for triggering muscular contraction. Another very important structure is the sarcomere. The sarcomere is the functional unit of striated muscle. CARDIAC MUSCLE Cardiac muscle forms the musculature of the heart. These muscles are striated and involuntary. Cardiac muscles are supplied by autonomic nerve fibers. Cardiac muscle contains elements of both striated skeletal muscle and smooth muscle.  The cells of cardiac muscle, known as cardiomyocytes, also appear striated under the microscope. Unlike skeletal muscle fibers, cardiomyocytes are single cells with a single centrally located nucleus. The striated structure of cardiac muscle is due to the arrangement of thick myosin and thin actin filaments which are similar to the arrangement of skeletal muscle. A principal characteristic of cardiomyocytes is that they contract on their own intrinsic rhythm without external stimulation. Cardiomyocytes attach to one another with specialized cell junctions called intercalated discs. Intercalated discs have both anchoring junctions and gap junctions. Intercalated disc attach cells form long, branching cardiac muscle fibers that act as a syncytium, allowing the cells to synchronize their actions. Gap junctions are situated adjacent to intercalated disks which is similar to those found in many smooth muscle cells. The cardiac muscle pumps blood through the body and is under involuntary control. In addition to other properties of muscle, the cardiac muscle properties also include conductivity and rhythmicity One percent of cardiac cells do not contract because the non-contracting cells have specialized features that aid in heart excitation. The non-contracting cells form a network known as the conducting system and contact other cardiac muscle cells at gap junctions. The conduction system begins the heartbeat and assists in spreading the contraction impulse rapidly. The present of intercalated disc causes the cells to behave like a functional Syncytium. The action potential of cardiac muscle is prolong due to presence of a plateau. Excitation contraction coupling is same as in skeletal muscles except for the fact that 20% of calcium needed for contraction enters the cell from the ECF during action potential. CYTOLOGY OF MUSCLE TISSUES Sarcolemma  The plasma membrane of a muscle cell Transverse (T tubules)  Tunnel in from the plasma membrane  Muscle action potentials travel through the T tubules Sarcoplasm, the cytoplasm of a muscle fiber  Sarcoplasm includes glycogen used for synthesis of ATP and a red-colored protein called myoglobin which binds oxygen molecules  Myoglobin releases oxygen when it is needed for ATP production Myofibrils  Thread like structures which have a contractile function Sarcoplasmic reticulum (SR)  Membranous sacs which encircles each myofibril  Stores calcium ions (Ca2+)  Release of Ca2+ triggers muscle contraction Filaments  Function in the contractile process  Two types of filaments (Thick and Thin)  There are two thin filaments for every thick filament Sarcomeres  Compartments of arranged filaments  Basic functional unit of a myofibril Z discs  Separate one sarcomere from the next  Thick and thin filaments overlap one another A band  Darker middle part of the sarcomere  Thick and thin filaments overlap I band  Lighter, contains thin filaments but no thick filaments  Z discs passes through the center of each I band H zone  Center of each A band which contains thick but no thin filaments M line  Supporting proteins that hold the thick filaments together in the H zone  FUNCTIONAL UNIT OF STRIATED MUSCLE The sarcomere is the functional unit of the muscle fiber. It is composed of overlapping units of two different filamentous proteins; the thick and the thin filaments. Movement of the thin filaments over the thick filaments brings about muscle shortening and force generation. Thus, the sarcomere is responsible for the contractile ability of muscle cells. The proteins found in the sarcomere can be placed into three proteins Contractile proteins Regulatory proteins Structural proteins The contractile proteins are actin (gives rise to the thin filaments) and myosin (give rise to thick) The regulatory proteins are tropomyosin (in the absence of Ca2+ , it covers the myosin – binding site of actin) and troponin (Ca2+sensor) Structural proteins are titin (provide elasticity), nebulin (run closely with actin) dydrophine, desmin (it binds z line with sarcomere) SLIDING FILAMENT MODEL OF CONTRACTION It state that when muscle fibers contract, the thin and thick filaments (A band) maintain the same length but the thin filament (actin filament) slide pass the myosin filament toward the center of the sarcomere. Due to these the Z-lines are drawn closer to the ends of adjacent A-band. Thus there is overall shortening of the myofibrils and thus of the muscle fibers A very important point to consider is that the tension generated in a muscle is directly proportional to the overlap between the thick and thin filaments. This extent of the overlap, of course, is a function of the number of myosin head groups that interact with thin molecules. The greater the overlap, the larger the tension that is developed by the muscle. It is possible for a muscle to generate tension without shortening. If one pushes against a wall, tension is generated without much skeletal muscle shortening. Note that this model is also called, Canoe and paddle, Walk along or ratchet theory of muscle contraction  SMOOTH MUSCLE Smooth muscle is situated in association with viscera. It is also called visceral muscle with each cell having a spindle shaped with a single nucleus. It has no cross striations, hence the name smooth muscle. Smooth muscle is supplied by autonomic nerve fibers. Smooth muscle contraction is responsible for involuntary movements in the internal organs. It forms the contractile component of the digestive, urinary, and reproductive systems as well as the airways and blood vessels. The function of smooth muscle is more difficult to examine due to several factors. First, due to lack of striation, smooth muscle ultrastructure is not as uniform and amenable to study as that of skeletal and cardiac myocytes. Second, the relatively weaker forces of contraction generated by smooth muscle (primarily because these are smaller cells) prevented a thorough characterization (at least in the early years when instrumentation was not as readily available as today). They lack sarcomeres and, therefore, the overlap of actin and myosin is not able to generate as much force as the much larger striated skeletal or cardiac muscle cells. The thin and thick filaments in the cytoplasm are arranged in long bundles that tend to follow oblique lines (diagonal) with respect to the long axis of the cell. Therefore, contraction of smooth muscle leads not only to shortening of the cell, but also leads to rounding of the cell (i.e., after contraction the cell assumes a globular shape). Both actin and myosin are present in smooth muscle. In addition, tropomyosin is present and associates with actin. However, troponin is absent in smooth muscle Twitches in smooth muscle cells can last much longer and are able to maintain tension for long periods of time than those of skeletal and cardiac cells. An important feature of smooth muscle cells is that they do not fatigue easily and can have a sustained contractions When smooth muscle cells undergo sustained contractions, they are said to have tone. Thus, when speaking of smooth muscle function, we must make distinction between tonic contractions and phasic contractions. Tonic contractions refer to some constant level of tension that is developed by the smooth muscle cell. An example would be in the walls of the arteries in which smooth muscle cells must tonically contract in order to maintain the tone of the artery wall. If the smooth muscle cells stimulated by the sympathetic nervous system (norepinephrine release), they will phasically contract in order to bring about vasoconstriction. Here, the force of contraction is increased transiently over its basal level. Smooth muscle contractions are very slow (0.5–5.0 s). Skeletal muscle contractions and relaxations last around 10–100 ms. Contractions of cardiac muscle cells can last 200–300 ms. Unlike skeletal muscle and cardiac muscle, recent studies suggest that some smooth muscle cells are able to give rise to new cells. In fact, it is thought that it is this property of smooth muscle that gives rise to pathological conditions such as arteriosclerosis. Transverse tubules (t-tubules) are absent in smooth muscle cells. Because smooth muscle cells are much smaller than cardiac and skeletal muscle cells, t-tubules are not necessary to spread the wave of depolarization deep within the cell. The sarcoplasmic reticulum of smooth muscle cells is not as well-developed as that of striated muscle. One reason for this is that Ca2+ is not the direct initiator of the cross-bridge cycle. Ca2+ however, serves as a second messenger signal in the cell and is still indirectly required in order to activate a cascade of events that lead to cross-bridge cycling. The amount of Ca2+ that is released from the sarcoplasmic reticulum of smooth muscle makes a small contribution to the total amount of Ca2+ needed to bring about contraction. The majority of Ca2+ enters from the extracellular space through plasma membrane Ca2+ channels. SMOOTH MUSCLE TYPES Smooth muscle are of two types: Single-Unit Smooth Muscle (or Unitary Smooth Muscle) Multi-Unit Smooth Muscle The cells of the single-unit smooth muscle type are electrically-coupled via gap junctions. Electrical coupling allows the activity of a group of muscle fibers to become coordinated (similar to the activity of the atria and ventricles of heart). Because the cells are electrically-coupled, individual cells in the group do not need to be innervated by the autonomic nervous system. Thus, innervation of only one or a few cells in the group is sufficient to control the activity of the entire group. The entire group that is connected by gap junctions is referred to as a functional syncytium. The cells of this smooth muscle type exhibit pacemaker potentials. Note that pacemaker potentials are unstable potentials that gradually depolarize to the threshold potential. Therefore, these cells exhibit spontaneous activity. Input of the nervous system is not required to initiate the contractions of these smooth muscle cells. Although single-unit smooth muscle cells are capable of spontaneous contractions, the level of the activity of the cells can be modified by the autonomic nervous system, i.e., they can be either inhibited or stimulated. Unitary smooth muscle lines the viscera (e.g., lining of the gastrointestinal tract, reproductive organs, urinary tract, and also some small blood vessels). Thus, it is also called visceral smooth muscle. Multi-Unit Smooth Muscle cells are not coupled via gap junctions. Multi-unit smooth muscle is found in the lining of blood vessels. Thus, it is also called vascular smooth muscle. It is also found in the lining of large airways to the lungs, muscles of the eyes used for accommodation, iris of the eye, sphincters and the base of the hair follicles. Muscular contraction is not spontaneous. Input from the autonomic nervous system is required for contraction. Each muscle cell has to be individually innervated. Therefore, contractile activity is said to be neurogenic. Both the parasympathetic and the sympathetic divisions of the autonomic nervous system are involved. The nervous input from these fibers can either inhibit or excite multi-unit smooth muscle cells. Differences between the muscles BRIEF DESCRIPTION OF THE STRUCTURE OF EXCITABLE TISSUES:- NERVE TISSUES  Nervous tissue is characterized as being excitable and capable of sending and receiving electrochemical signals that provide the body with information.  Two main classes of cells make up nervous tissue: the neuron and neuroglia.  Neurons propagate information via electrochemical impulses, called action potentials, which are biochemically linked to the release of chemical signals.  Neurons possesses the property of irritability and conductivity  They respond to various types of stimuli  They are distributed throughout the body as an integrated network  Neuroglia play essential roles in structurally and physically supporting neurons, stabilizing synapses, and modulating their information propagation. 20   Neurons display distinctive morphology, well suited to their role as conducting cells, with three main parts:  The cell body (soma) includes most of the cytoplasm, the organelles, and the nucleus.  Dendrites branch off the cell body and appear as thin extensions. They transfer the incoming signals to the soma.  A long “tail,” the axon, extends from the cell body and can be wrapped in an insulating layer, called myelin, formed by neuroglia. It carries the outgoing action potential away to another excitable cell. The cell body contains the nucleus and a nucleolus and it is the major biosynthetic center  It is also the focal point for the outgrowth of neuronal processes, and contain Contains an axon hillock – cone-shaped area from which axons arise  The cell body lack centrioles (hence its amitotic nature) but contain prominent basophilic Nissl bodies (rough ER)  The cytoskeleton of neuron is formed by microtubules & neurofilaments  Myelinated axons are called tracts in the CNS and nerves in the PNS Axons split into multiple axon terminals when they are close to their target. At the end of each terminal is a synaptic knob that will pass the electrical signal to the next cell (usually another neuron, muscle fiber, or gland) by stimulating the release of a neurotransmitter There is usually only one unbranched axon per neuron The movement of impulse along axons occurs in two ways – Anterograde — toward the axon terminal – Retrograde — toward the cell body The dendrites are short, tapering processes and branch extensively to form “Dendritic tree”  They are the receptive or input regions of the neuron and lack Golgi complexes. Generally, neurons are classified based on: Structural classification Functions Presence or absence of myelin There are two major types of glial cells in the vertebrate nervous system: microglia and macroglia. Microglia are scavenger cells that resemble tissue macrophages and remove debris resulting from injury, infection, and disease (eg, multiple sclerosis, AIDS-related dementia, Parkinson disease, and Alzheimer disease). Microglia arise from macrophages outside of the nervous system and are physiologically and embryologically unrelated to other neural cell types There are three types of macroglia: oligodendrocytes, Schwann cells, and astrocytes. Oligodendrocytes and Schwann cells are involved in myelin formation around axons in the CNS and peripheral nervous system, respectively. Astrocytes, which are found throughout the brain, are of two subtypes. Fibrous astrocytes, which contain many intermediate f laments, are found primarily in white matter. Protoplasmic astrocytes are found in gray matter and have a granular cytoplasm. Both types send processes to blood vessels, where they induce capillaries to form the tight junctions making up the blood–brain barrier  SYNAPSE Synapse is the junction between two neurons. It is not an anatomical continuation. But, it is only a physiological continuity between two nerve cells. Nerve impulse is transmitted from one neuron to other through neurotransmitters Synapse is classified by two methods: A. Anatomical classification B. Functional classification. The anatomical classification are axoaxonic synape, axodendritic synapse, axosomatic synape The functional classification is on the basis of mode of impulse transmission. According to this, synapse is classified into two categories: 1. Electrical synapse 2. Chemical synapse. Chemical synapse: Almost all the synapses used for signal transmission in the central nervous system of the human being are chemical synapses. In these, the first neuron secretes at its nerve ending synapse a chemical substance called a neurotransmitter (or often called simply transmitter substance) The transmitter in turn acts on receptor proteins in the membrane of the next neuron to excite the neuron, inhibit it, or modify its sensitivity in some other way. Some examples of neurotransmitters are acetylcholine, norepinephrine, epinephrine, histamine, gamma- aminobutyric acid (GABA), glycine, serotonin, and glutamate. In the chemical synapse, there is no continuity between the two neurons because of the presence of a space called synaptic cleft between the two neurons. Electrical synapses: Electrical synapse is the synapse in which the physiological continuity between the presynaptic and the postsynaptic neurons is provided by gap junction between the two neurons. There is direct exchange of ions between the two neurons through the gap junction. Important feature of electrical synapse is that the synaptic delay is very less because of the direct flow of current. Moreover, the impulse is transmitted in either direction through the electrical synapse. This type of impulse transmission occurs in some tissues like the cardiac muscle fibers, smooth muscle fibers of intestine and the epithelial cells of lens in the eye. FUNCTIONS OF SYNAPSE Main function of the synapse is to transmit the impulses, i.e. action potential from one neuron to another. However, some of the synapses inhibit these impulses. So the impulses are not transmitted to the postsynaptic neuron. On the basis of functions, synapses are divided into two types: 1. Excitatory synapses, which transmit the impulses (excitatory function) 2. Inhibitory synapses, which inhibit the transmission of impulses (inhibitory function). Sequence of events during synaptic transmission. Ach = Acetylcholine, ECF = Extracellular fluid, EPSP = Excitatory postsynaptic potential.  Inhibition of synaptic transmission is classified into five types: 1. Postsynaptic or direct inhibition 2. Presynaptic or indirect inhibition 3. Negative feedback or Renshaw cell inhibition 4. Feedforward inhibition 5. Reciprocal inhibition. Sequence of events during postsynaptic inhibition. GABA = Gamma-aminobutyric acid, ECF = Extracellular fluid, IPSP = Inhibitory postsynaptic potential.