BIOL 233 4.7 Synaptic Signaling PDF

Synaptic Signaling BIOL 233 Lecture 4.7 Dec. 4 (last lecture!) Last Lecture Outline! 1. Review of action potentials 2. Neurotransmitter release from pre-synaptic neurons 3. The neuromuscular junction 4. Mechanism of muscle contraction 5. The sarcolemma  Review of Action...

Synaptic Signaling BIOL 233 Lecture 4.7 Dec. 4 (last lecture!) Last Lecture Outline! 1. Review of action potentials 2. Neurotransmitter release from pre-synaptic neurons 3. The neuromuscular junction 4. Mechanism of muscle contraction 5. The sarcolemma  Review of Action Potentials What is the mechanism for neurotransmission? 1. Pre-synaptic neuron  neurotransmitter release 2. Synaptic cleft  ligand-gated ion channel receptors on post-synaptic neuron. 3. Membrane depolarization opens voltage-gated ion channels 4. If stimuli strong enough, depolarization  axon terminal 5. Pre-synaptic neuron  neurotransmitter release  Review of Action Potentials What is membrane potential? RMP is maintained by? Types of K+ channels? Types of Na+ channels?  Review of Action Potentials What is membrane potential? Ion concentration difference across plasma membrane RMP is maintained by? Na+/K+ pumps  3 Na+ pumped out & 2 K+ pumpe in. Types of K+ channels? Leakage (essential for AP) & Voltage-Gated Types of Na+ channels?  Review of Action Potentials Inactivation gates plug what type of channels? What are absolute versus relative refractory periods? What is meant by ”all or none?” How is strong stimuli coded?  Review of Action Potentials Inactivation gates plug what type of channels? Voltage-gated Na+ channels What are absolute versus relative refractory periods? Absolute = no amount of stimuli can trigger an AP Refractory = only strong stimuli can trigger an AP What is meant by ”all or none?” APs are the same no matter how strong the stimuli How is strong stimuli coded? More frequent APs and recruitment of other axons  Neurotransmitter Release Presynaptic neuron Neurotransmitters are packaged in synaptic vesicles These are anchored to plasma membrane by SNARE proteins For membrane fusion: requires Ca2+ binding protein synaptotagmin Postsynaptic neuron  Neurotransmitter Release Presynaptic neuron In resting neurons: low intracellular Ca2+ Synaptotagmin inactive  no interactions with SNAREs Postsynaptic neuron Neurotransmitter Release Action Potential  Na+ influx Membrane depolarizes opens VG Ca2+ channels Ca2+ influx activates synaptotagmin  that activates SNAREs Vesicles fuse with plasma membrane  Glutamate & Acetylcholine Glutamate: most abundant excitatory neurotransmitter in brain & spinal cord (central nervous system) Acetylcholine: most abundant neurotransmitter in peripheral nervous system (outside CNS). Controls muscle contraction! Muscle Contraction: Neuromuscular Junction (NM Motor neurons release ACh from their “end plates” (axon terminals) muscle fibers Muscle Contraction: Neuromuscular Junction (NMJ Ca++ Ion Channels Vesicles w/ acetylcholine Motor Neuron Neuromuscular Junction Skeletal Muscle Fiber Muscle Contraction: Neuromuscular Junction (NMJ Remember: muscle contraction driven by interactions between myosin & actin filaments Muscle contraction requires Ca2+ Ca2+ binding to troponin complex moves tropomyosin Exposes myosin-binding sites Muscle Contraction: Neuromuscular Junction (NM What state is a muscle in when Ca2+ is low? Ca2+ is stored in muscle cells in the sarcoplasmic reticulum ACh  AChR. Depolarizes sarcolemma Stored Ca2+ released into the muscle cell cytoplasm What does Ca2+ do to actin filaments? What happens to muscle?  Muscle Contraction: Mechanism 1. Axon terminal releases Ach 2. Ligand-gated AChRs 3. Ion-gated Na+ influx further depolarizes sarcolemma  cascade of VG Na+ channels opening  Muscle Contraction: Mechanism 4. Intracellular Ca2+ released 5. Ca2+ binds to actin-bound troponin 6. Moves tropomyosin 7. Myosin binds and ?  The Sarcolemma Transverse tubules (T- tubules) Ca2+ channels: Ryanodine Receptors in SR membrane.  Common Disorders of the NMJ: Muscular Dystrophy Large group of X-linked muscle mutations Mutations of dystrophin protein Normal dystrophin: links F-actin to the ECM  Common Disorders of the NMJ: Myasthenia Gravis Most common NMJ Disease Autoimmune disease Immune system attacks AChRs Anti-AChR antibodies present in sera Treatment: Acetylcholinesterase  Common Disorders of the NMJ: Botulism Toxin Bacteria binds to pre-synaptic axon terminal Enters via receptor-mediated endocytosis  cleaves SNARE complex Muscle Contraction Video Link https://vimeo.com/garlandscience30308032/review/ 136842711/46f52fb5cd