Structure & Function Lect # 2 Excitable Tissue Prof Kumlesh K. Dev Department of Physiology Four Tissue Types 1. Epithelial tissue Lining/barrier of secretory Skin and mucous membranes 2. Muscle (excitable) tissue Skeletal (striated) Smooth Cardiac 3. Nervous (excitable) tissue Brain Spinal cord 4. Connective tissue (cells, fibres, matrix) Loose connective tissue Dense fibrous tissue (Capsule, Ligament, Tendon) Cartilage & Bone Blood (originate from bone marrow) Types of Muscle Types of Muscle Skeletal Striated Cardiac Unstriated Smooth Specialised for contraction to produce force and movement (n.b. generates heat) 1. Smooth - weaker, continuous contractions - cells, central nuclei 2. Cardiac - strong, continuous contractions - fibres (branching), striations, central nuclei Voluntary Involuntary 3. Skeletal - strong, short contractions - fibres, striations, peripheral nuclei 1
(1) Smooth Muscle function & feature little/weak contractile apparatus long, slender, spindle shaped cells single central nucleus no myofibrils = nonstriated composed of thick filaments thin filaments located in organs of cardiovascular system respiratory system digestive system urinary system reproductive system (2) Smooth Muscle innervation involuntary (autonomic innervation) dual (stimulatory/inhibitory) y) graded, spreading & continuous contraction multi-unit each cell innervated variable force e.g. airways, large arteries single-unit few cells directly innervated synchronous contraction (myogenic) e.g. gut, uterus Types of Muscle (1) Cardiac Muscle Specialised for contraction to produce force and movement (n.b. generates heat) 1. Smooth - weaker, continuous contractions - cells, central nuclei function and feature all-or-none ( twitch ) continuous, rhythmic activity resistant to fatigue Cardiac Purkinje fibres Pale (unstained glycogen). 2. Cardiac - strong, continuous contractions - fibres (branching), striations, central nuclei 3. Skeletal - strong, short contractions - fibres, striations, peripheral nuclei innervation involuntary pacemaker cells coordinate contraction of tissue electrical conduction (Purkinje fibres and gap junctions) SA Node AV Node Purkinje fibres 2
(2) Cardiac Muscle Types of Muscle cardiocytes are cardiac cells contain myofibrils = striated cells contact each other at intercalated discs cells bound together by - gap junctions - desmosomes Specialised for contraction to produce force and movement (n.b. generates heat) 1. Smooth - weaker, continuous contractions - cells, central nuclei 2. Cardiac - strong, continuous contractions - fibres (branching), striations, central nuclei 3. Skeletal - strong, short contractions - fibres, striations, peripheral nuclei (1) Skeletal Muscle (2) Skeletal Muscle composed of skeletal tissue connective tissue nerves blood vessels functions movement supports viscera maintain body temperature store nutrients features long, unbranched fibres many peripheral nuclei contractile apparatus - actin and myosin - striations - powerful contraction single innervation (one nerve ending per fibre) all-or-none twitch/contraction 3
(3) Muscle-fibre types (properties) (4) Skeletal Muscle: formation Type I Type II Muscle fibers develop through the fusion of Myoblast mesodermal cells SDH mitochondrial enzyme activity matpase activity (anaerobic) oxidative capacity (aerobic) capillaries speed of contraction resistance to fatigue high low high slow high low high low fast low (5) Skeletal Muscle: organisation (6) Fascicle (bundle of fibers) collagen fibres (epimysium, perimysium, endomysium) )blend dto form tendon at end tendons attaches skeletal to bone fascicle = bundle of fibers d f l composed of several cells (fibers) epimysium surrounds entire endomysium surrounds individual fibers perimysuim surrounds each fascicle Tendon 4
(7) Muscle Cell/Fiber (8) Myofibril cells make individual fibers fiber cells are large and elongated have multiple peripheral nuclei produce voluntary contractions myofibrils composed of myofilaments EM of skeletal X 26 000 (9) Myofilaments (Myosin/Actin) (10) Skeletal Muscle: summary myofilaments/sarcomeres composed of thick filament myosin thin filaments actin during contraction sarcomere shortens myosin-binding protein C binds myosin and actin striations due to alignment of filaments of myofibrils Sarcomere Z line H zone I band A band ted H zone shorter I band shorter A band same width Z line relaxation contraction Sarcomere shorter Thick filament Thin filament 5
Four Tissue Types 1. Epithelial tissue Lining/barrier of secretory Skin and mucous membranes 2. Muscle (excitable) tissue Skeletal (striated) Smooth Cardiac 3. Nervous (excitable) tissue Brain Spinal cord 4. Connective tissue (cells, fibres, matrix) Loose connective tissue Dense fibrous tissue (Capsule, Ligament, Tendon) Cartilage & Bone Blood (originate from bone marrow) (1) Nervous System: divisions CENTRAL NERVOUS SYSTEM (CNS) BRAIN SPINAL CORD THE NERVOUS SYSTEM PERIPHERAL NERVOUS SYSTEM (PNS) CRANIAL NERVES SPINAL NERVES SOMATIC NERVOUS SYSTEM (SNS) AUTONOMIC NERVOUS SYSTEM (ANS) (2) Four Major Brain Cells Blood Brain Barrier brain is a very complex organ huge number of specialised cells forming a huge number of connections. cell types neurons astrocytes microglia glial oligodendrocytes (CNS) schwann Cells (PNS) Astrocyte release growth factors, create scar tissue, control BBB Neuron Capillaries form the bloodbrain-barrier (BBB) Oligodendrocyte provide Myelin sheaths that insulate axons Axon Myelin sheath Microglia the macrophages of the brain, provide an immune system against infections but release molecules that kill neurons Astrocyte Basement membrane Neuron blood vessel lumen Lymphocyte, Monocyte, Neutrophil Pericyte pericyte is a mesenchymal-like cell can differentiate into fibroblast, smooth cell, or macrophage Endothelial cell Tight junction 6
(3) Neuronal Components (4) Classification: structural soma cell body dendrites receive information axons conduct info. away synapse where two neurons meet myelin sheath protective neuronal covering Nucleus Arrows indicate the direction in which nerve signals are conveyed. Input Zone Dendrites and Cell body Trigger Zone Axon hillock Conducting Zone Axon (may be from 1mm to more than 1m long) Output Zone Axon terminals in Unipolar Neuron in Bipolar Neuron in Multipolar Neuron one branch out out out morphologies differ in shape, size, processes by number of branches directly from cell body unipolar (1 branch) biopolar (2 branches) ) multipolar (many branches) (5) Classification: functional (6) Neurotransmission Sensory neurons nerves that make you feel deliver info from sensory receptors in PNS to CNS Motor neurons nerves that make you move deliver motor commands from CNS to PNS,, glands Communicate with each other Communicate with s Communicate with glands 1. action potentials reach presynaptic terminal 2. stimulate Ca 2+ entry 3. neurotransmitters released from synaptic vesicles 4. neurotransmitter crosses synaptic junction (synapse) 5. on postsynaptic terminal transmitter binds receptor 6. receptor activated to transmit a signal in postsynaptic neuron 7
(7) Action potential conduction velocity (8) Presynaptic Transmitter Release Unmyelinated Fibre - depends on - fibre diameter -slow (<1 m/s) Myelinated Fibre - depends d on - fibre diameter - inter-nodal distance - fast (up to 120 m/s) Myelin sheath Axon Oligodendrocyte Schwann cell CNS PNS Node of Ranvier synaptic vesicles 40-60 nm diameter concentrated in clusters at nerve terminals neurotransmitter release involves 1. targeting of SVs to release sites 2. docking of SVs to plasma membrane 3. priming to fuse SVs during impulse 4. fusion/exocytosis & transmitter release 5. retrieval of SV by endocytosis kiss & run process SVs recycle without collapsing into memb. Golgi Targeting Docking/ Priming Axon Fusion Exocytosis (Kiss & Run) synaptophysin Retrieval Terminal (9) Postsynaptic Receptor Activation (10) Neurotransmitters and Receptors 1. Neurotransmitters bind receptors 2. Receptors are then activated 3. Activation of Receptors transmits signal into the cell 4. signals cause the cell to grow, die, move, etc Many drugs work by binding receptors Agonist drugs activate receptors like neurotransmitters Antagonists drugs inhibit receptors and block neurotransmitters binding to receptors action potential presynaptic neuron what neurotransmitter? e.g. Acetylcholine Neurotransmitter release action potential synapse postsynaptic neuron what receptor? Target cell responds e.g. Cholinergic Nicotinic & Muscarinic 8
(11) Major Neurotransmitters Major neuroransmitters of the PNS - Acetylcholine - Noradrenaline (Norepinephrine) p - Adrenaline (Epinephrine) Major neurotransmitters of the CNS - Glutamate - Gamma-aminobutaric acid (GABA) Others major neurotransmitters - Dopamine - Serotonin (5 HT) - Histamine (12) Sensory Receptors Sensory receptors provide sensations of taste, pressure, pain, touch, temperature, sight, smell, hearing, body position External Internal Chemoreceptors Taste/Smell O2/C02, ph Thermo receptors Skin Deep in CNS Osmo receptors Blood osmolarity Photoreceptors t Rods & Cones Nociceptors nerve ending pain Mechanoreceptors Touch / Pressure, Muscle length, joint Balance, Motion, Hearing position, blood pressure Electroreceptors Magnetoreceptors (13) Neurotransmitters and Receptors (14) Body Sensory Afferents: to feel postganglionic parasympathetic fibres release act on muscarinic receptors postganglionic sympathetic fibres release noradrenaline acting on α/β adrenoreceptors on sweat glands acts on muscarinic receptors on renal system Dopamine acts on dopaminergic receptors motor nerve fibres leaving CNS release acting on nicotinic receptors al Crani Thoracolumbar Sacral CNS Pre-ganglionic Ganglion Post-ganglionic parasympathetic sympathetic sympathetic sympathetic N N sympathetic (adrenal medulla) N motor (somatic) Cardiac & smooth, gland cells, N M nerve terminals Cardiac & smooth NA, gland cells, α/β nerve terminals M D N D 1 adrenaline N Sweat glands Renal vascular SM Released into blood Skeletal, acetylcholine NA, noradrenaline D, dopamine N, nicotinic M, muscarinic α/β, adrenergic Afferents: Body to Brain Sensory system is composed of 3 neurons 1oy Primary Neuron Synapse 2oy Secondary Neuron (runs up to thalamus) Synapse 3oy Tertiary Neuron (runs up to cortex) interpretation occurs in cortex from body cortex peripheral nerves 1oy 3oy 2oy thalamus 9
(15) Body Motor Efferents: to move Synaptic Junctions Efferents: Brain to Body Motor system is composed of 3 neurons cortex 1. Upper Motor Neurons (UMN) (in cortex) Synapse 2. Middle Motor Neurons (MMN) (in spinal cord) Synapse UMN nerve-glands (we won t cover) 3. Lower Motor Neurons (LMN) (leave spinal cord) innervate s to s peripheral nerves PNS LMN MMN nerve-nerve (general synapse) nerve- (neuromuscular junction) (1) Generalised Synapse (2) Neuromuscular Junction Key features nerve-nerve synapse smaller than a NMJ with a narrower synaptic cleft smooth postsynaptic membrane gives small surface area may be excitatory or inhibitory numerous transmitter substances Key features NMJ is larger than a nerve-nerve synapse with a wider synaptic cleft folds of postsynaptic membrane gives larger surface area the NMJ is always excitatory only one transmitter Acetylcholine Axon of motor neuron Myelin sheath Axon terminal Vesicle of acetylcholine Acetylcholine receptor Acetycholinesterase Motor end plate Action potential propagation in motor neuron Action potential propagation in fiber Contractile elements within fiber 10
(3) Motor end plate potential (MEPP) (4) Motor end plate potential (MEPP) Large, myelinated (alpha) axons innervate s Muscle Miniature End Plate Potentials (MEPPs) Motor end plate is where Ach binds receptors One motor endplate per fibre Spontaneous release of Ach give a small miniature end plate potential (MEPP) Action potential propagation in fiber Membrane Potential (mv) Membrane Potential (mv) +30 0-90 +30 0 no summation needed 1 2 3 4 Time (ms) +Curare ( receptor antagonist) motor end plate Motor end plate Contractile elements within fiber -90 EPP 1 2 3 4 Threshold Time (ms) A Motor unit is composed of one motor neuron and all fibres it innervates all fibres of a motor unit will contract together providing stronger force (5) Motor Unit A Motor unit one motor neuron can innervate many fibers (promiscuous) one fiber is only innervated by one motor neuron (6) Motor Unit A large Motor Unit may have more > 1000 fibres e.g. biceps A small Motor Unit may have as few as 10 fibres e.g. eye 11
(7) Toxins affecting NMJ transmission (8) Comparing Synapses Curare - irreversibly Blocks Ach receptors Botulinum toxin - blocks Ach release Black Widow venom - excess release of Ach - continuous contraction Organophosphates (Pesticides/Nerve Gas) - irreversibly blocks acetylcholine-esterase preventing breakdown of Ach - continuous contraction Motor end plate Contractile elements within fiber Action potential propagation in fiber Nerve - Nerve Synapse nerve-nerve synapse smaller than a NMJ with a narrower synaptic cleft smooth postsynaptic membrane gives small surface area may be excitatory or inhibitory numerous transmitter substances potential is lower - always subthreshold summation needed Neuromuscular Junction NMJ is larger than a nerveih a wider synaptic cleft nerve synapse with folds of postsynaptic membrane gives larger surface area the NMJ is always excitatory only one transmitter Acetylcholine potential is higher - always suprathreshold no summation needed Myasthenia gravis - autoimmune disorder Myasthenia gravis - treatment - 200 400 cases per million - body makes antibodies that attack nicotinic receptors at NMJ - smaller End Plate Potential which may be sub-threshold - fewer Action potentials in so contractile force is reduced - muscular weakness develops Symptoms - eye weakness - weakness of other limbs - respiratory s may need intubation to maintain airway Treatments - cholinesterase inhibitors eg neostigmine - Immunosuppressants 12
Learning Outcomes (Lessons 5 & 6) To be able to: 1. describe the structure and function of the different types of Smooth, cardiac, skeletal (type of contraction, innervation etc) 2. comment on their appearance in section Position and rel. size of nucleus (presence/absence in profile) 3. describe the fibre-types of skeletal Type I, II, enzymes, properties. 4. define a motor unit All the fibres supplied by a single neurone 5. describe the structure t and function of a neurone Processes, nuclear form, nucleolus, granules 6. describe myelinated and nonmyelinated nerve axons. Myelin: wrapping of cell membrane (lipid) 13