Neuromuscular Physiology PDF

Neuromuscular Physiology Associate Professor Christian Moro  Before a skeletal muscle fiber can contract, it must receive an impulse from a nerve. This occurs at the neuromuscular junction. For a nice overview (not required to read): https://www.ncbi.nl...

Neuromuscular Physiology Associate Professor Christian Moro  Before a skeletal muscle fiber can contract, it must receive an impulse from a nerve. This occurs at the neuromuscular junction. For a nice overview (not required to read): https://www.ncbi.nlm.nih.gov/books/NBK470413/ Image: Marieb, E. N., & Hoehn, K. (2022). Human anatomy and physiology (12th ed.). Pearson Regulation of skeletal muscle contraction All skeletal muscle is activated by nerves Skeletal muscle cells each receive nerve input from somatic nervous system motor neurons (via CNS) The location where the nerve terminal meets the muscle cell is called the neuromuscular junction Comprises: - Nerve terminal of motor neuron axon (presynaptic component) - Synaptic cleft - muscle cell membrane (motor end plate). (postsynaptic component) All neurons innervating skeletal muscle release the neurotransmitter acetylcholine (ACh) ACh activates nicotinic receptors on the muscle - generates an action potential in muscle - ultimately leads to contraction Excitation-contraction coupling This slide is revision from your MEDI11-101 Week 11 session: “Physiology of excitable tissues”. We return to this topic again in MEDI12-201 The next 3 slides show the same thing, just in slightly different angles Illustration: Marieb, E. N., & Hoehn, K. (2022). Human anatomy and physiology (12th ed.). Pearson Illustration: Marieb, E. N., & Hoehn, K. (2022). Human anatomy and physiology (12th ed.). Pearson  Neuromuscular junction Illustration: Marieb, E. N., & Hoehn, K. (2022). Human anatomy and physiology (12th ed.). Pearson Illustration: Marieb, E. N., & Hoehn, K. (2022). Human anatomy and physiology (12th ed.). Pearson Revision: Membrane Potential The voltage difference exists only at the membrane – The cell interior is electrically neutral if you add up all the negative and positive charges in the whole cytoplasm K+ and negatively-charged proteins predominate inside body cells, whereas the extracellular fluid contains relatively more Na+ – This is largely balanced by Cl- The plasma membrane is somewhat permeable to the K + but the protein anions cannot follow it through. As such, the continual loss (leakage) of positive ions from the inside of the cell makes the membrane interior more negative. At a certain point, the negative charges inside the cell become large enough to attract the external K + back inside… this occurs at -90mV and is the point where the concentration gradient is exactly balanced by the electrical gradient At this point… every potassium that enters the cell is followed by one leaving. Sodium can also contribute to the RMP and in some cells the Na + is attracted to the interior by its concentration gradient, and this brings the RMP to -70mV. Cl- is also present but its entry into the cell is resisted by the negative internal charges  Peripheral nervous system - motor division Skeletal muscle’s neuromuscular junction (NMJ) Cell bodies in central Neurotransmitter nervous system Peripheral nervous system at effector Single neuron from CNS to effector organs ACh NERVOUS SOMATIC SYSTEM Two-neuron chain from CNS to effector organs SYMPATHETIC ACh NE Smooth muscle’s NMJ is less Ganglion structured Autonomic fibers branch diffusely PARASYMPATHETIC ACh ACh to form diffuse junctions Ganglion Illustration: Marieb, E. N., & Hoehn, K. (2022). Human anatomy and physiology (12th ed.). Pearson Smooth muscle (not really a structured NMJ) Smooth muscle is innervated by autonomic nervous system neurons No ‘highly structured’ neuromuscular junctions Axons of nerves innervating smooth muscle have swellings (varicosities which contain neurotransmitters Neurotransmitter released into ‘diffuse’ area Illustration: Marieb, E. N., & Hoehn, K. (2022). Human anatomy and physiology (12th ed.). Pearson Peripheral nervous system - motor division Illustration: Marieb, E. N., & Hoehn, K. (2022). Human anatomy and physiology (12th ed.). Pearson  Myasthenia Gravis Autoimmune disease where the immune system makes antibodies against the acetylcholine receptors on muscle cells Blocks the actions at the receptors and prevents the signal to be received by the muscle cell the neuromuscular junction. Photo: Beverly Hills Neurology Excitation-contraction coupling Electrical signal (nerve AP) chemical signal (ACh)  electrical signal (Muscle AP)  chemical signal (Ca2+)  contraction Put all steps together - i.e. excitation/contraction coupling + cross bridge cycling + reuptake of calcium - relaxation Photo by C. Moro Excitation-contraction coupling – in steps - Process whereby action potential in motor neuron produces contraction of muscle cell 1. Action potential conducted along motor neuron and arrives at nerve terminal 2. Depolarisation of membrane potential opens voltage-gated Ca2+ channels 3. Ca2+ enters nerve terminal and causes synaptic vesicles to fuse with synaptic membrane 4. ACh is released from vesicles and crosses synapse to bind with receptors on the motor end plate (ACh receptors are chemical-gated ion channels) 5. Binding of ACh changes shape of receptor - opens channel 6. Na+ ions flow through channels into cell causing depolarisation of the motor end plate 7. Depolarisation of motor end plate initiates an action potential in the sarcolemma Excitation-contraction coupling 8. Action potential transmitted via T tubules to the sarcoplasmic reticulum 9. Action potential causes Ca2+ release from SR 10. Ca2+ binds to the troponin complex on thin filaments and changes shape 11. Change in tropomysin conformation reveals binding sites for myosin 12. Cross bridge cycling occurs - muscle contracts 13. After action potential ends, Ca2+ actively pumped back into SR 14. Tropomyosin block of myosin-actin binding is restored 15. Contraction ends and the muscle relaxes Additional Resources on muscle (all shorter than 5 mins) Christian’s TED-Ed Muscle Fatigue Video − Over 5 million views – check it out! Skeletal Muscle vs Smooth Muscle Click the link to view the video What is Muscle Fatigue?  Click the link to view the video Additional muscle contraction videos & tips on Christian’s Instagram @physiologywithchristian – pop by and say hi! Happy studying!