Neurones and Glia MD224 PDF

NEURONES AND GLIA MD224 Professor Karen Doyle Neurophysiology [email protected] Neurons Cell body Dendrites Axon Electrically excitable Ca++ Na+ Movement of ions • Diffusion through ion channels • Active transport/ facilitated diffusion ClK+ Membrane potential • Nerve an...

NEURONES AND GLIA MD224 Professor Karen Doyle Neurophysiology [email protected] Neurons Cell body Dendrites Axon Electrically excitable Ca++ Na+ Movement of ions • Diffusion through ion channels • Active transport/ facilitated diffusion ClK+ Membrane potential • Nerve and muscle cells are electrically excitable • Electrical current results from movement of ions across membrane https://opentextbc.ca/anatomyandphysiology/chapter/12-4-the-action-potential/ Membrane potential • Voltage difference across a cell membrane • At rest, called resting membrane potential » EM • Unequal distribution of ions (Na+, K+, Cl-) across cell membrane • Greater permeability to K+ than Na+ • Large anions inside cell • Na+ /K+ electrogenic pump (3 Na+ out, 2 K+ in) » Inside made negative relative to outside • Resting membrane potential generally between -60 to -80 mV Membrane potential • Voltage difference across a cell membrane • At rest, called resting membrane potential » EM • Unequal distribution of ions (Na+, K+, Cl-) across cell membrane • Greater permeability to K+ than Na+ • Large anions inside cell • Na+ /K+ electrogenic pump (3 Na+ out, 2 K+ in) » Inside made negative relative to outside • Resting membrane potential generally between -60 to -80 mV Resting membrane potential • Uneven distribution of ions at rest Extracellular Intracellular (mmol/L) Na+ ClK+ 150 110 5 15 10 150 • Concentration gradient • Electrical gradient Equilibrium potential – Unequal distribution of ions (Na+, K+ , Cl- ) across membrane » Concentration gradient » Electrical gradient • Ions diffuse along concentration gradient (e.g K+ out) • When concentration gradient for K+ = electrical gradient pulling K+ in, the result is the equilibrium potential for K+ • Equilibrium potential for all ions can be predicted using Nernst equation EK+=RT loge [K+]o zF [K+]i Membrane potential • Voltage difference across a cell membrane • At rest, called resting membrane potential » EM • Unequal distribution of ions (Na+, K+, Cl-) across cell membrane • Greater permeability to K+ than Na+ • Large anions inside cell • Na+ /K+ electrogenic pump (3 Na+ out, 2 K+ in) » Inside made negative relative to outside • Resting membrane potential generally between -60 to -80 mV Na+ /K+ electrogenic pump Ion channels • Composed of protein subunits • Voltage gated • Ligand gated • Mechanosensitive Action potential Action potential • • • • Threshold All or nothing Self-propagating Refractory period Action potential • • • • Threshold All or nothing Self-propagating Refractory period Threshold: All or nothing +15mV 99 • Voltage-gated Na+ channels • Depolarisation • Activation gate – Threshold ~ +15mV to RMP • Inactivation gate – Refractory period » Absolute » Relative – Up to x5000 increase in Na+ conductance at AP • Voltage-gated K+ channels • Repolarisation Action potential • • • • Threshold All or nothing Self-propagating Refractory period Local circuits • Adjacent areas reach threshold • Propagation of AP • Refractory period facilitates AP propagation in one direction only Refractory period X Unmyelinated axon Saltatory conduction Myelinated axon Refractory period X • Na+ influx depolarises the cell for up to 3 mm along axon • Distance between nodes of Ranvier Myelin • Glia – PNS: Schwann cells – CNS: Oligodendrocytes • Layers containing sphingomyelin • Nodes of Ranvier • 1-3mm intervals • Saltatory conduction • Current flows through extracellular fluid and axoplasm from node to node Classes of nerves • Diameter • Conduction velocity – Myelin • Myelinated • Unmyelinated – General classification • A (a, b, g, d) •B •C – Sensory nerve classification • I (A, B), II, III, IV Classes of nerves Synaptic transmission • AP propagation to axon terminal • Activation of voltage-gated Ca++ channels • Ca++ activates Ca++-calmodulin- dependent protein kinase II • Primes vesicles for mobilisation, docking to release sites on presynaptic membrane and membrane fusion • Exocytosis Synaptic transmission Axons to Dendrites • Most transmission is axodendritic Receptors • Ionotropic • Protein subunits arranged around a pore • Fast activation • Short duration of action • Metabotropic • G-protein linked • Slow activation • Long duration of action Post synaptic potentials – Excitatory neurotransmitters produce depolarisation of the postsynaptic membrane • Excitatory postsynaptic potential – An EPSP may favour an action potential, but is not in itself one • No propagation • Graded responses obtainable – Inhibitory neurotransmitters produce hyperpolarisation of the postsynaptic membrane • Inhibitory post synaptic potential • An IPSP makes it more difficult to trigger an action potential Summation of post synaptic potentials can occur at the axon hillock Spatial and temporal summation Spatial Temporal Www.cabrillo.cc.us/~dscott/bio5/lectures Glia • Greek for glue • Protectors and support cells of neurons • Heighten the functional capacity of neurons Schwann cells Oligodendrocytes Astrocytes Ependymal cells Radial glia Microglia Glial functions • Myelin • Schwann cells (PNS) • Oligodendrocytes (CNS) • Control of extracellular environment around neurons • Astrocytes • Ependymal cells • Brain development • Radial glia • Immune function • Microglia Glia • 10-50x more glia than neurons • Microglia are derived from macrophages outside of CNS • Phagocytes; activated by infection and injury • Macroglia (all other groups) are derived from neural stem cells Macroglial functions • Structural support • Insulate axons • Blood brain barrier • Release growth factors to nourish and protect neurons – Neurotrophins eg GDNF • Guide migrating neurones and axon outgrowth • Synaptogenesis • Promote efficient signaling between neurons – Clear neurotransmitter from synapses eg glutamate – Respond to neuronal signaling by releasing glial factors Macroglia have a crucial role in the anatomical development of the brain Created with BioRender.com NAdr Ach DA https://www.freepik.com/ Role of glia in synaptogenesis • Neurons migrate during development but synapse formation only occurs when astrocytes (or other macroglia) are present – Extracellular protein signals from astrocytes – Trigger synapse formation in CNS – Adult hippocampal stem cells display similar dependence on astrocytes for synapse formation • Macroglia are also necessary for synapse maintenance Macroglia • Astrocytes and other macroglia actively control synaptogenesis – Regulate synapse number – Regulate synapse stability – Regulate synapse function • Evidence that schwann cells in the periphery trigger neuromuscular junction formation Role in synaptic activity • Glia in culture sense synaptic activity – Calcium transient currents • Release gliotransmitters in response to neuronal activity