MD137 Muscle Lecture2 PDF - University of Galway Physiology

Physiology School of Medicine 2024 Skeletal Muscle: structure & function II MD137:Principles of Lecturer: Dr K.McCullagh Physiology Describe the steps of electrical activation of muscle contraction - excitation contraction coupling. E...

Physiology School of Medicine 2024 Skeletal Muscle: structure & function II MD137:Principles of Lecturer: Dr K.McCullagh Physiology Describe the steps of electrical activation of muscle contraction - excitation contraction coupling. Explain how the neuromuscular junction works and clinical relevance. The Neuromuscular junction (NMJ) NMJs SKELETAL MUSCLE FIBERS SOMATIC MOTOR NEURON (AXON)  Excitation Contraction Coupling Represents physiologic mechanism whereby an electrical discharge at muscle initiates chemical events at cell surface to release intracellular Ca2+ and produce muscle action Excitation Contraction Coupling Motor Axons and NMJs Neuromuscular Junctions and Motor End Plates  Neuromuscular Junctions and Motor End Plates Neuromuscular junction: site where a motor neuron stimulates a muscle fiber Motor end plate: area of the muscle fiber sarcolemma where a motor neuron stimulates it  The Neuromuscular Junction 8 Structural features of the neuromuscular junction  Electrical activity at the neuromuscular junction End Pate Depolarization below Potential (EPP) threshold to activate Na+ channels and so Excitatory no AP is formed Postsynaptic EPSP Potential Electrical activity at the neuromuscular junction. (cont.) -55mV -70mV EPSP EPSP -70mV EPSP  Clinical Implications Any substance that affects Acetycholine transmission will affect muscle contraction Botulism toxin (BOTOX) used for Focal Dystonias, Spasticity in cerebal palsy & Cosmetic surgery (Inhibits acetylcholine release from nerve terminal) Curare used on poison arrows in South America (Blocks AChR receptor) Acetycholinesterase inhibitors for Myasthenia gravis (grave muscle weakness) “Botox Capital” of the World – Westport, Ireland January 16, 2017  Myasthenia gravis (grave muscle weakness) UCGH Patient Autoimmune disease: Immune from Prof G.Loftus system does not recognise the ACh Receptors as self and so attacks and diminishes the density of these receptors at the NMJ. Incidence 1:5000 Acetycholinesterase inhibitors for Myasthenia gravis (e.g. Neostigmine). (see next slide) Plasmapheresis (plasma exchange) is also type of treatment for autoimmune diseases such as myasthenia gravis  Acetycholinesterase inhibitors Inhibition of Acetycholinesterase -> less degradation of ACh. ACh increases in the synaptic cleft and compensates for the low numbers of Ach Receptors Excitation Contraction Coupling Sarcoplasmic Reticulum (SR) Opening  Transverse Tubules Narrow membranous tunnels formed from the sarcolemma Open to the extracellular environment Able to conduct action potentials  Sarcoplasmic Reticulum (SR) SR is modified endoplasmic reticulum that stores Ca2+ when muscle is at rest. When a muscle fiber is stimulated, Ca2+ diffuses out of the SR via calcium release channels (Ryanodine receptor; RyR). At the end of a contraction, Ca2+ is actively pumped back into the SR by the Ca2+- ATPase pump. Myofibrils and Sarcoplasmic Reticulum (SR)  Excitation-Contraction Coupling Dihydropyridine Ca-ATPase pump constantly 30% of ATP active to tightly regulate calcium levels 70% of ATP Vander’s Human Physiology, 15th Ed.2019  Stimulating a Muscle Contraction Acetylcholine is released from the motor neuron. End plate potentials are produced. Action potentials are generated. Voltage-gated calcium channels (DHPR) in transverse tubules change shape and cause calcium channels in SR to open. Calcium is released and can bind to troponin C Cross-bridges bind, rotate and generate force (70% ATP)  Muscle Relaxation Action potentials cease. Ca2+-ATPase pumps Ca2+ back into SR (30% ATP). No more Ca2+ is available to bind to troponin C, so no more cross bridges are formed. Excitation Contraction Coupling Temporal sequence of events in excitation-contraction coupling (msec) 100ms An Action Potential precedes the rise in Ca2+, which precedes cross-bridge cycling resulting in force development