Nerve-Muscle Physiology (MSc DAN 2024-25) PDF

05-09-2024 3. Nerve – Muscle Physiology...

05-09-2024 3. Nerve – Muscle Physiology 3.1. Describe the structure of a neuron NERVE MUSCLE PHYSIOLOGY 3.2. Explain the significance of myelin sheath 3.3. Explain the concept and ionic basis of RMP 3.4. Describe the nerve action potential and its ionic basis 3.5. Classify muscles and tabulate the differences between them 3.6. Describe the structure of skeletal muscle Dr. Shreevatsa Bhat M 3.7. Describe the neuromuscular transmission in skeletal muscle Division of Physiology Dept. of Basic Medical Sciences 3.8. Explain excitation-contraction coupling in skeletal muscle MAHE-Manipal [email protected] 3.9. Describe the causes and features of multiple sclerosis & myasthenia gravis STRUCTURE OF A MULTIPOLAR NEURON Motor neuron with a myelinated axon The neuron (nerve cell) is the fundamental unit of the nervous system. INITIAL The basic function of a neuron is to receive information send a signal to other CELL BODY SEGMENT MYELIN NODE OF SCHWANN OF AXON CELL neurons, muscles, or glands. SHEATH RANVIER A multipolar neuron is a type of neuron that its cell body possesses a single axon and many dendrites Examples for multipolar neurons are Motor neurons AXON HILLOCK Interneurons of the brain and the spinal cord. NUCLEUS TERMINAL A motor neuron is composed of: BUTTONS NISSL GRANULES Nerve cell body (soma) Processes: dendrites and axon DENDRITES Myelin sheath SCHWANN CELL Saltatory conduction in myelinated neuron AXON Continuous conduction in unmyelinated neuron Myelin is a protein–lipid complex that is wrapped around the axon It is formed by Schwann cells in the peripheral nervous system (PNS) and by oligodendrocytes in the central nervous system (CNS) 1  05-09-2024 Resting Membrane Potential (RMP) Myelin is an effective insulator Definition: RMP is the potential difference across the cell membrane at rest, Ionic conductance occurs only in nodes of Ranvier as Na+ channels are with inside negative relative to the outside concentrated here In neurons the RMP is about: -70mV Impulses in myelinated neuron jumps from one node of Ranvier to the next In a muscle cell the RMP is: -90mV (saltatory conduction) Significance: Myelinated axons conduct impulses faster than unmyelinated fibers Destruction of myelin (demyelination) in the CNS which is associated with delayed or blocked conduction. Genesis/Ionic basis of RMP: Nerve excitability Nerve cells respond to electrical, chemical, or mechanical stimuli More K+ efflux occurs during rest compared to Na+ influx (There are more open K+ channels than Na+ channels at rest and hence permeability to K+ is greater) Physiochemical disturbances: Contribution of 3Na+ 2K+ATPase pump: It pumps 3Na+ ions to the exterior in exchange for only 2K+ ions Local, non-propagated potentials (graded, synaptic, generator potentials) Large, non-diffusible negatively charged proteins inside the cell Propagated potentials All above mechanism generates negativity inside cell during rest (Action potentials or nerve impulses) Action potential +30 Overshoot Membrane potential (mV) Action potential is a rapid change in membrane potential which propagates as an 0 impulse along the membrane of excitable cells A threshold stimulus is required to develop an action potential Threshold potential (firing level) -55 Threshold potential The electrical events in neurons are rapid and measured in milliseconds (ms) -70 RMP Hyperpolarization RMP Initial depolarization The potential changes are small and measured in millivolts (mV). Depolarizing stimulus Time (ms) 2  05-09-2024 Ionic basis of different phases of AP Rapid depolarization: (-55 to +30mV) Rapid Na+ influx due to opening of many voltage gated Na+ channels causes RMP (-70mV) rapid upstroke in the membrane potential Due to continuous K+ leakage during rest Peak value: (+30mV) Inactivation and closure of voltage-gated Na+ channels stops the Na+ influx Initial depolarization: (-70 to -55mV) In response to a stimulus, initially only few voltage-gated Na+ channels open Repolarization phase: (+30 to -70mV) and few amount of Na+ enter the cell Voltage gated K+ channels start to open and K+ efflux starts Threshold potential: (-55mV) Hyperpolarization: (-70mV to more –ve) 15 mV change in membrane potential in response to a threshold stimulus. It continuous efflux of K+ due to prolonged opening of K+ channels opens many voltage gated Na+ channels by positive feedback (firing level) Voltage gated K+ channels close and bring the AP to an end. And, RMP is restored by Na+K+ pump MUSCLE: TYPES & FEATURES Features Skeletal muscle Cardiac muscle Smooth muscle location Attached to Heart muscle Forms hollow visceral skeleton organs Striations Striated Striated Nonstriated Nerve supply Somatic Autonomic Autonomic Control Voluntary Involuntary Involuntary Autorhythmic No Yes Yes Shape of the Long cylindrical Short cylindrical Spindle shaped muscle fiber unbranched branched unbranched Present & functions as Present & functions as Gap junctions Absent syncytium syncytium Sarcomere Well developed Well developed Poorly developed Troponin Present Present Absent Fatigability Can be fatigued Cannot be fatigued Can be fatigued Structure of Skeletal Muscle 3  05-09-2024 Sarcomere Thin filament Thick filament Neuromuscular junction structure Neuromuscular transmission Arrival of an action potential at the motor nerve ending Opening of voltage gated Ca2+ channels prejunctional membrane Influx of Ca2+ in to the nerve terminal Fusion of vesicle to the prejunctional membrane Exocytosis & release of acetylcholine into the synaptic cleft Excitation contraction coupling Acetylcholine binds to its receptors on the motor end plate Opening of ligand gated Na+ channels It is the process by which depolarization of muscle fiber initiates contraction Influx of Na+ in to the muscle cell It comprises the electrochemical changes occurring in the Depolarization motor end plate nerve, NMJ and muscle in response to stimulus Generation of end plate potential (EPP) Ca2+ play important role Action potential develops and spread over sarcolemma 4  05-09-2024 Excitation contraction coupling and Tropomyosin moves away from actin & Mechanism of skeletal muscle contraction uncover the myosin-binding sites Development of an action potential (AP) at sarcolemma Myosin with ATP binds to actin and Inward spread of AP along T tubules ATP split into ADP + Phosphate and releases energy AP reaches terminal cisterns of Myosin heads rotate and move the attached actin sarcoplasmic reticulum (power stroke) Release of Ca2+ from sarcoplasmic reticulum Thin filaments slide-over/walk-along thick filament Ca2+ diffuses in to myofilaments and binds to troponin C Shortening of sarcomere and muscle contraction Steps in relaxation of skeletal muscle Myasthenia gravis Cause Myasthenia gravis is an autoimmune disease caused by the destruction of Ca2+ pumped back into sarcoplasmic reticulum ACh receptors due to the formation of antibodies to ACh receptors Failure of neuromuscular transmission due to reduction in ACh receptors Release of Ca2+ from troponin Features Cessation of interaction between actin and myosin Fatigue of extraocular muscles & weakness in eyelid Difficulty in speech Weakness in respiratory muscles & respiratory failure Relaxation of the muscle Treatment By using cholinesterase inhibitors (e.g. neostigmine) Multiple sclerosis Cause Multiple sclerosis is an autoimmune disease that develops antibodies that destroy the myelin sheath in the CNS Features: associated with delay or block in conduction Lower limb weakness, spasticity, and exaggerated reflexes Numbness Urinary incontinence Blurred vision, altered color perception, and defective field of vision painful eye movements, difficulty in speech and swallowing 5