Physiology 210 Nerve and Muscle PDF

Physiology 210 Nerve and Muscle Simon Gosgnach 3-020D Katz Group Building [email protected] Textbook: Vander’s Human Physiology. Material for exam from notes/lecture, textbook a good source of reference. and b Chapters 9 - - - 2-3 10 = per lecture 15 questions The Stretch Reflex frovels...

Physiology 210 Nerve and Muscle Simon Gosgnach 3-020D Katz Group Building [email protected] Textbook: Vander’s Human Physiology. Material for exam from notes/lecture, textbook a good source of reference. and b Chapters 9 - - - 2-3 10 = per lecture 15 questions The Stretch Reflex frovels bute =- • • • • GOAL: obtain a mechanistic understanding of a simple reflex behaviour. How is information produced, transmitted, processed along nervous system pathways? Model system: Patellar-tendon stretch reflex (Knee-jerk reflex) a monosynaptic reflex. Function? Book example- We dont We think react in that about how situation as it just happen Neil ~ Stretcheee Withdrawal reflex ↳touching a hot store Material to be covered: • • • ~Stretch reflex GOAL: obtain a mechanistic understanding of a simple reflex behaviour. NERVE • • • • • Components of the nervous system, neuronal structure. Membrane structure of a neuron, pumps, channels, resting membrane potential. How an action potential is generated. How an action potential is transmitted. How the action potential travels between neurons. MUSCLE • • SYNAPSE How the signal travels from neuron to muscle. How the electrical signal is converted into a mechanical movement (i.e. muscle contraction). Learning Objectives 1. Be able to identify the different components of the CNS and PNS. 2. Be able to identify the different cell types of the CNS and describe their function. 3. Be able to identify the components of a reflex loop and how they interact to generate a simple reflex. 4. Be able to identify and describe the function of each component of a neuron. Components of the nervous system. • • • Central Nervous System Cerebral cortex Cerebellum Brainstem Spinal cord • • • • - Back of cortex Peripheral Nervous System (PNS) peripheral nerves • More to come regarding brain structures in CNS lectures. Cells of the nervous system. • Neurons (10% of cells in CNS; occupy 50% of the volume). • Each either interneuron inhibitory excitetory is 3 types of neurons. • Afferent neurons carry information from periphery to the spinal cord via the dorsal roots. EXCITATORY • Efferent neurons carry information from the spinal cord to the periphery via the ventral roots.EXCITATORY • of . ~ Can be inhibitory Interneurons carry information between neurons. EXCITATORY OR INHIBITORY ↳ completely enclosed • or exciteson C in : all components Glia (meaning glue): • • • • Provide structure/support isolating neurons from one another (satellite cells). Produce myelin (oligodendrocytes in the CNS, Schwann cells in the PNS). Guide migrating neurons and direct axonal outgrowth during development (radial glia). Form the blood brain barrier (astrocytes). E · Satulite Cells structure + Support - >insulating so that current adoes not lave the cell Spinal cord: interface for reflexes • spinal cord 3 types of neurons. • dorsal roots (sensory) ventral roots (motor) Afferent neurons carry information from periphery to the spinal cord via ↳ the dorsal roots. afferent fibre CNS • • Efferent neurons carry information from the spinal cord to the periphery via the ventral roots. efferent fibre Interneurons carry information between neurons. vertebra 6 E Split around off s . C. I mixed peripheral nerve Both Afferents and Efferents Spinal cord: interface for reflexes spinal cord -activated receptor afferent fibre Afferent dorsal horn (sensory) -lot Reflex Loop of myelinated aro white matter (nerve fibres, glia) -7 Call bodius + Waste grey matter (neurons, glia, synapses) muscle efferent fibre ventral horn (motor) Efferent Neuron structure/polarity dendrites direction of flow ↓receiveSigne cell body e nucleus presynaptic axon hillock first segment ↳determines general of axun is cell postsynaptic will Art-P axon presynaptic synaptic terminals Will not flow from back cell to bodies Cell bre postsynaptic Neuron structure Types of Neurons A. Bipolar cell doesnt really E dendrites have B. Pseudo-unipolar cell taking into from photoreceptor -> goes to ganglia A P ~Wheregenerater . cell I Stereotypical Nauron ~ laidone functio C. Multipolar cells one is ↳ dendrites very denstinctions ~ A point where Separated ↳into Retina P Ganglion cell of dorsal root ntral Co · axon ~ cell Body S. Motor neuron of spinal cord Pyramidal cell of hippocampus Purkinje cell of cerrebellum e Interneurons ↳ perihex e INS Entierly within ne very specialized Neuron structure ~20-40 yum in astoligodendri (mine diamet A pre en Learning Objectives 1. Be able to identify the different components of the CNS and PNS. 2. Be able to identify the different cell types of the CNS and describe their function. 3. Be able to identify the components of a reflex loop and how they interact to generate a simple reflex. 4. Be able to identify and describe the function of each component of a neuron. Material to be covered: • • • GOAL: obtain a mechanistic understanding of a simple reflex behaviour. NERVE • • • • • Components of the nervous system, neuronal structure. Membrane structure of a neuron, pumps, channels, resting membrane potential. How an action potential is generated. How an action potential is transmitted. How the action potential travels between neurons. MUSCLE • • SYNAPSE How the signal travels from neuron to muscle. How the electrical signal is converted into a mechanical movement (i.e. muscle contraction). Learning Objectives 1. Be able to identify structure and components of the neuronal cell membrane. 2. Understand the role of the Na+K+ pump in setting the resting membrane potential. 3. Describe how the electrical and chemical gradients of Na+ and K+ across the neuronal membrane maintain the resting membrane potential. How charge separation bu in faut of call breaks dow Membrane Structure - axon axon cell body dendrites * Ions Phospholipid Bilayer: impermeable barrier cannot pass by Hemselves through A •Protein pumps and channels: •control movement of ions through membrane. -specific ions •Pumps: Active transport & Nat K + & -Hydrolysis of ATP •Ion Channels •Passive Channels (leak •Gated Channels •Ligand-gated •Voltage-gated 3Nat out 2 k in - chemical Electrogradient -> Allow based in ~ synaptic let takes transmission >electro change channels) ↳ always ↳ on Up it something to open thm I - * closed & rest must reach certain Resting Membrane Potential (Em) • Measure of electrical potential difference between intracellular environment and extracellular environment. • Resting membrane is approximately -70mV. • Ions primarily involved in setting resting membrane potential • K+, Na+ • Pumps/channels primarily involved in setting resting membrane potential • Na+/K+ exchanger, Na+ leak channels, K+ leak channels. 0 Na+ -K+- - Na+ - K+Na+ -70 - K+- Cl- K+- K+ K+ Na+ K+ - - Cl- ClNa+ K+ K+ Cl- Na+ Cl- K+ Na+ Na+ Na+ Resting Membrane Potential (Em) axon axon cell body dendrites Phospholipid Bilayer: impermeable barrier Will mostly never have RMP &- 70 that usually around my •Protein pumps and channels: •control movement of ions through membrane. Nat It , •Pumps: Active transport Move Ions-> 3 Nat out for akt in gradient •Ion Channels •Passive Channels (leak •Gated Channels •Ligand-gated •Voltage-gated ↳ Without regard channels) Net - charge is set by Na+/K+ pump • • Na+/K+ pump is electrogenic, as it moves charge across the membrane. Requires energy which is obtained from the hydrolysis of ATP (an energy carrying molecule) to ADP + P • 3 Na+ molecules move out of cell and 2 K+ molecules move into the cell. • Results in a net negative charge inside cell. Sodium * fairly Ions & ↑Potassium pump opens inside and -outside of closes Inside * Fons to cell, to outside . ~ Sodium comes out prosobat 2 Recent Closed to inside of Cell, open to outside 2 It come in and bind pottasium outsi posit vany" leads I a = to uneva stiwe im key for gradient Na+ K+ K+ Cl- - little 3 Both 0 Phosphat Na+ -K+- - Na+ - K+Na+ -70 - K+- Cl- K+- K+ K+ Na+ K+ - - Cl- Cl- still Open & little Sodium of cell Na+ Cl- K+ Na+ Na+ Na+ -tries to go back to Equilibrium Na+/K+ pump creates gradients. me Chemical Gradients Chemical Gradient wit K+ K+ Nat W Na+ Na+ Nat gradient kt Nat wants diffuse out of call K+ wants to diffuse out of the cell. wants to to to diffuse in the cell Na+ wants to diffuse into the cell. Electrica I I . Intracellular Enviornment Electrical Gradient Si -- --- ++ + - -- ++ + -- Over time wants to become more positive inside relativy"-"compared to outside Intracellular environment wants to become more positive. Resting Membrane Potential (Em) axon axon cell body dendrites Phospholipid Bilayer: impermeable barrier lak •Protein pumps and channels: •control movement of ions through membrane. channel ↳ Specific for kt ↳ Are always movement ↳ open through ECG Nat and + always them acts ↳ attempt Eq •Pumps: Active transport allow on to by leak each go Ion back to going through Channels own •Ion Channels •Passive Channels (leak •Gated Channels •Ligand-gated •Voltage-gated channels) Em is set by leak channels. • Leak channels- always open. • Allow passive flow of ions into/out of the neuron. • • - If more T -N - H is They are selective- each ion has its own leak channels through which only they can pass. more to put go K+ - 2 forces acting on each ion • chemical gradient • electrical gradient ↳wants • EXAMPLE #1 K+ • Equilibrium potential for K+: approximately -90mV around ~ • - - go ↳wants · net - charge net + charge out >pushing chemical force So et electrical force "t" charge inside mid e K+ leak channel Equilibrium potential: the membrane potential at which the chemical concentration gradient is balanced. equal K+ and happy - nee Will t want to move Em is set by leak channels. • Leak channels- always open. • Allow passive flow of ions into/out of the neuron. • They are selective- each ion has its own leak channels through which only they can pass. • I -E more "t" to ↳want If leave -" more Wante to enter He net - charge - see Na+ - 2 forces acting on each ion • chemical gradient • electrical gradient EXAMPLE #2 Na+ ~ can calculate * wars using V • -Always Equilibrium potential for Na+: +60mV. fairly Electrochemical and forces equal to are each chemical force Na+ electrical force Na+ leak channel all • net + charge positive opposite o Equilibrium potential: the membrane potential at which the chemical concentration gradient is balanced. Em is set by leak channels. • • Alone Na+ would force RMP to +55 mV Alone K+ would force RMP to -90 mV • Both Na+ and K+ are present in nerve cells: what happens to Em? • RULE: The more permeant the ion, the greater its ability to force Em towards its own equilibrium potential. Resting Membrane Potential Em is set by leak channels. • RULE: The more permeant the ion, the greater its ability to force Em towards its own equilibrium potential • Permeability is 50-100x greater to K+ than Na+. G • Em is therefore closer to EK+ 2 K+ - EK= Em= -90mV -70mV 0 ENa= +60mV K+ - Na+ - K+ K+ K+ K+ Review of Resting Membrane Potential. - Activity of Na+/K+ ATPase causes intracellular environment to be negatively charged with respect to extracellular environment (3Na+ out/2 K+ in). - Leak channels (always open, selective) allow diffusion of ions down their electrical and chemical concentration gradients in an attempt to reach equalibrium. E K+ C E Na+ C K+ Equilibrium potential for K+=-90mV Na+ Equilibrium potential for Na+= +55mV 3 usually ↳ futile on membrane stays own potential study & -70m2 ↳ combined effort At resting membrane potential passive ionic fluxes are balanced so that there is charge separation and Em remains constant. Value of resting membrane potential (-70mV) is closest to equilibrium potential of ion with greatest membrane permeability (K+). -> Tested em eten. Not m Sodium K+ A- Na+ Cl- Na+ Cl- Pottusium Concentrations & Ion [extracellular] mM [intracellular] mM Na+ 150 15 K+ 5 150 120 10 - 100 ClK+ and ↑ has almost no setting organic anion role membraa • Resting membrane potential -70 due to Na+/K+ pump and leak channels ot Ilakput of Throug Channel & ⑰ lea - 1 Nat all out Potential Enegy - membrane ↳ - Enembrane layroom I Goes " " thoug of Wat leak channel ↳ into kt Cell P 0 Ru · -70mV At all times by RMPStays &-70 -time mV membrane Rm is determined permeability to Nat and t Comes from membrane ↳ leads to AP ↑ Action Potential) Material to be covered: • • • GOAL: obtain a mechanistic understanding of a simple reflex behaviour. NERVE • • • • • Components of the nervous system, neuronal structure. Membrane structure of a neuron, pumps, channels, resting membrane potential. Nat How an action potential is generated. permeability massivley How an action potential is transmitted. How the action potential travels between neurons. -) MUSCLE • • inc .. for SYNAPSE How the signal travels from neuron to muscle. How the electrical signal is converted into a mechanical movement (i.e. muscle contraction). Lecture Objectives: 1a. Understand how an action potential is generated and the importance of threshold, the depolarizing phase, the repolarizing phase, afterhyperpolarization, and refractory period. 1b. Be able to identify the ion channels responsible for each of these events. 2. Understand the process of electrotonic conduction. 3. Understand the role of myelin and be able to explain the process of saltatory conduction. The Stretch Reflex • • GOAL: obtain a mechanistic understanding of a simple reflex behaviour. How is information produced, transmitted, processed along nervous system pathways? At rest : me efferent Afferent , . • all Model system: Patellar-tendon stretch reflex (Knee-jerk reflex) a monosynaptic reflex. & interneurons -70mV What tendon happens is when tapped ? Action Potentials still • movement of ions in fout all X Resting membrane potential: steady state condition determined by relative permeability of membrane to Na+ and K+ . • Specific stimuli (physical or chemical) disrupt this steady state by causing ion-selective channels in membrane to open. ~ Open Nut channels in membrane ↳ depolarization • Two main types of ion channels (in addition to leak channels) • voltage-gated ion channels I • ligand-gated ion channels • An electrical signal, known as an action potential is generated due to (become Important for generating AP more it - closed & rest activity of voltage-gated Na+ and voltage-gated K+ channels. Opening of these channels results in ions flow and membrane potential changes. • ACTION POTENTIAL: a large change in membrane potential from -70mV to +30mV and back to resting over a period of a few ms. axon axon cell body dendrites Phospholipid Bilayer: impermeable barrier •Protein pumps and channels: •control movement of ions through membrane. Closed & - When a Rm rest reaches Certain value - •Pumps: Active transport - Channel opens •Ion Channels •Passive Channels (leak •Gated Channels •Ligand-gated •Voltage-gated channels) How are afferents activated? •Muscle stretch (stretch reflex) or other stretch receptor sensory stimuli results in increased opening of specialized Na+ receptors, entry of Na+ into afferent fibre and depolarization of afferent neuron. - ion •If Na+ entry is sufficient to depolarize the muscle stretch neuron to its threshold (~-50mV) the result is the opening of voltage gated Na channels and an action potential. - mechanically opening channels Stretched muscle ↳ Nat Can ↳into Streteceptor , ex : in this attached to afferent down gradients all Cdepolarization) - if depolarized enough ↳ leads O- more electrochemical stretch receptor gated to Voltage-gated ion channels meane •Membrane depolarization •Depolarization results in opening of voltage gated Na+ channels. removes activation gate, allows Na+ to flow into cell. •Influx of Na+ into cells (inc Nat . permeability) brings membrane potential closer to Na+ equilibrium potential (+55mV). •Open conformation is only maintained for a few ms. Inactivation gate then closes channel. Depolarization results in opening of voltage-gated K+ channel and voltage activated a repolarization. stuggered Na+ Na+ voltage-gated - I voltage-gated Outside Na+ channel K+ channel but same is Cell : +- L +- opening be Kt W phospholipid bilayer +Inside cell activation gate +I flow I of Na blocked activation gate loca u inactivation gate Gossette - K+ opens up When depolarized K+ ↳ allows out of Ru k5 cell to -> flow return to ( channel Slower opens mechanically Action Potentials: Summary I I - +30 Closing Nat of Voltage gated channels opening & " "K"channels ⑧ depolarization stimulus causes . threshold : gatachment VoltageNat gated channels s 3 + Voltage-gated Nat channel -55mV gates open Voltage-gatedkt channels are activation open 15 open - membrane morei . are Nat Channels are inactivating potential than Voltage-gated K channels are still open , Nat channels hib is open Dua too AD Channels leak it voltage open ↳ Condition , gated Pushes Ray to be more : in resting state e Nat channels closed Reason for change in P 1. Rest the channels are are eventuallyItVoltagedete Channels closed and Rm - 70mV Relative Permeability K+>>Na+ 2. Depolarizing input 3. Start of AP (depol) 4. Repol phase sensory or synaptic stim. V-gated Na+ channels open V-gated K+ channels open & Na+ channels inactivate to Na+ Na+ >>>>K+ K+>>>>Na+ 5. End of AP V-gated Na+ channels at rest V-gated K+ channels still open K+>>>>Na+ 6. Rest V-gated K+ channels at rest K+>>Na+ of threshold Absolute - Impossible to fire another AP refrac periodory Relative refractory period . - possible to but difficult generate an AP . Material to be covered: • • • GOAL: obtain a mechanistic understanding of a simple reflex behaviour. & NERVE • • • • • Components of the nervous system, neuronal structure. Membrane structure of a neuron, pumps, channels, resting membrane potential. How an action potential is generated. How an action potential is transmitted. How the action potential travels between neurons. MUSCLE • • SYNAPSE How the signal travels from neuron to muscle. How the electrical signal is converted into a mechanical movement (i.e. muscle contraction). Action Potentials: Transmission. synt or portrigt Action Potentials: Transmission. Axon ++++++++++ +++++++++++++++ ------------------------------------------------------------------------++++++++++ +++++++++++++++ Voltage-gated Na+ channels 1. Axon at resting membrane potential. Action Potentials: Transmission. Axon ---------------+++++++++++++++ +++++++++ -----------------------+++++++++ --------------------------------------+++++++++++++++ Voltage-gated Na+ channels 1. Axon at resting membrane potential. 2. Activation results in opening of voltage-gated Na+ channels, local depolarization of membrane. Action Potentials: Transmission. e A generate -----------++++++++ +++++++++ ------------+++++++-----------e Axon ------------+++++++----------------------++++++++ +++++++++ Voltage-gated Na+ channels 1. Axon at resting membrane potential. 2. Activation results in opening of voltage-gated Na+ channels, local depolarization of membrane. 3. Local depolarization of membrane causes adjacent voltage-gated Na+ channels to activate. 4. New action potential is generated in adjacent membrane. 5. Action potential only travels in one direction due to refractory period. *Electrotonic Conduction. 2 30 mu Electrotonic Conduction. Spread of current inside axon = electrotonic conduction Summary: AP initiated at one point in membrane Current spreads electrotonically to adjacent membrane Adjacent membrane depolarizes to threshold New AP generated in adjacent membrane Electrotonic conduction proceeds in one direction only due to refractory period. A travels AWAy from cell buy + 30m Peak of AD Idepolariation ~ Electrotonic Conduction. Speed of AP conduction: Important??? Electrotonic current flow is fast but AP must be regenerated at every point on the membrane. This requires opening and closing of channels which takes time! How can speed of AP propagation be increased??????? Myelination Cells of the nervous system. • Neurons (10% of cells in CNS; occupy 50% of the volume). • • 3 types of neurons. • Afferent neurons carry information from periphery to the spinal cord via the dorsal roots. EXCITATORY • Efferent neurons carry information from the spinal cord to the periphery via the ventral roots.EXCITATORY • Interneurons carry information between neurons. EXCITATORY OR INHIBITORY Glia (meaning glue): • • • • Provide structure/support isolating neurons from one another (satellite cells). Produce myelin (oligodendrocytes in the CNS, Schwann cells in the PNS). Guide migrating neurons and direct axonal outgrowth during development (radial glia). Form the blood brain barrier (astrocytes). Myelination Myelination increases speed of electrotonic conduction. It is formed from: Schwann cells in peripheral nervous system Oligodendrocytes in central nervous system on only around the myelin a -I-era Myelination is discontinuous: Nodes of Ranvier Myelination is discontinuous: Nodes of Ranvier Schwann cell (PNS) Motoneuron 0.1-1mm axon cell body axon terminals Nodes of Ranvier Oligodendrocyte (CNS) Many Schwann cells ensheath 1 axon in the PNS. One Oligodendrocyte ensheaths many axons in the CNS. Saltatory Conduction. Myelination increases speed of conduction by increasing efficiency of electrotonic conduction such that AP need not be regenerated at every part - of the axonal membrane. Simple depolarization across neighbouringtissue . Instead AP is regenerated at nodes of Ranvier but current flows electrotonically between nodes. This process = saltatory conduction throbbing Classification of afferent fibre type. ↑ Shar duller Painonset i n ↳ Slower ↓ Fibre type Group I Group II Group III Group IV Diameter 12-20um 6-12um 1-5um 0.2-1.5um 35-75m/s 5-30m/s 0.5-2m/s Cond. Speed 80-120m/s Sensory receptors skeletal muscle give proprioceptor Action Potential frequency Fast ↳ feedback des/ob ; eck skin =Bumping mechanoreceptor int Constant pain/temperatur pain/itch/temp e erature Unmielinated ~ Slow Saltatory Conduction. AP arrives at axon going from left to right Why does AP conduct in only one direction Speed of AP conduction: Myelinated axons: 12-130 m/sec (45-450 km/h) Unmyelinated axons: 0.5-2 m/sec (15-60 km/h) * myelinated unmyelinated travels an faster Absolute refractory period lasts almost 2 msec By the time the absolute refractory period is over, AP is between 2 and 20 cm down the axon I Material to be covered: What ILind myelinate • • • of girl an all inhibitory interneurons I GOAL: obtain a mechanistic understanding of a simple reflex behaviour. NERVE • • • • • Components of the nervous system, neuronal structure. Membrane structure of a neuron, pumps, channels, resting membrane potential. How an action potential is generated. Electrotonic important A Saltatony us ~ How an action potential is transmitted. How the action potential travels between neurons. MUSCLE • • angelinate Myelin , neurose oligodendrocytes Schwann calls SYNAPSE How the signal travels from neuron to muscle. How the electrical signal is converted into a mechanical movement (i.e. muscle contraction). will , Lecture Objectives: 1. Compare and contrast chemical and electrical synaptic transmission. 2. Be able to identify each of the steps involved in chemical synaptic transmission. 3. Understand what is meant by temporal summation and spatial summation of PSPs 4. Understand the difference between PSPs and action potentials. Synaptic Transmission. mee Sensory neuron fires AP in response to physical stimulus which causes a receptor potential, nerve ending depolarizes to threshold, AP generated in sensory neuron AP travels via electrotonic or saltatory conduction to synaptic terminals in CNS No direct connection between sensory neuron to muscle therefore have to get message across gap How does message get from one cell to the next? ↓ conductor myelinated "thick interneuron transmitter Synaptic Transmission. ~No ~ V chemical f naptic y S -ransmission I Electrical Synaptic Transmission red here Electrical Synapses. · · no clear Connexing pre/post - Synaptic transmission forms Physical coupling bir/pre/post alls Functional significance of electricalgene convulsions disense synapses? Synapse Early -> Development ↳ of Ns Not , always Embryogenesis terminal Fast of -> Fon flow from - - - - pre-post or post - Pre , can also get Canything that can and another other things fits through connexing pass during Synapse can be point bi cell body call along any of the neuron E Bidirectional Communication b/w cytoplasm for sharing regulatory signals Connexins ↳what Neuroscience 2nd Ed. Purves et al (2001) do they do ? Chemical Synapses ↓Pre-sync ~post-synapti e Chemical Synapses ~larger in gap seen Chemical Synapse bu pre/post-synaptic -> Rather than coupling Neuroscience 2nd Ed. Purves et al (2001) all Chemical Synapses: directly-gated. •Transmitter binds to Ly receptor on channel Fan •Receptor channel opens •Ions pass through channel •(K+ and Na+) or Na+ only = excitatory = EPSP Neurotransmitter binds ~ Excitatory on vesicle ↳ sitsane ~Transmitter icet Synaptic 21-8175-3 to achiev equilibrium •Cl- or K+ pass through = inhibition to neurotransmitters = IPSP - potential ↳ Inhibitory Post Synaptic - Funotropic receptor • Effects are fast in onset and short lasting (msec) ↳ if if channel may repolarize ↑for a short to equilibrium • Receptor and effector molecule Selective amt ->-7um of time are same - Excitatory Inhibitory NT-7 NT-> ↑ Cl or I out of bods Glutamate Articholin , GABA , Funchannel rically depolarized : opens On ~ n -60 cell is a Lbc the n effe Glycine lit Have e * showe to release bth axon axon cell body dendrites Phospholipid Bilayer: impermeable barrier •Protein pumps and channels: •control movement of ions through membrane. •Pumps: Active transport •Ion Channels •Passive Channels (leak Channels -•Gated •Ligand-gated •Voltage-gated Ionotropic - Channel receptors channels) Chemical Synapses: indirectly-gated. * Trigge Metaboli ↳ * Receptor ene T located on Ion Channel •Transmitter binds •Activates N & - ↳ activates 2nd messenger system I much N W multiple intracellular actions occur befor stuer process Cell membrane 2nd messenger system (via G proteins; GTP activates adenylyl cyclase which converts ATP to cAMP, the 2nd messenger) Synapse ↓ occurs I •cAMP activates protein kinases which phosphorylate channel and cause it to open or close, causing change in membrane permeability. •ions flow, depol or hyperpolarization •*slow onset, long lasting; *receptor and effector are different molecules. Chemical Synapses vs. Electrical Synapses. ~cannot mode e i Remember: electrical are inflexible - great for stereotypical behaviors but difficult to change. Chemical synapses provide flexibility Inhibition: only possible with chemical synapses Specificity: specific transmitters have specific effects on postsynaptic membrane Complexity: type, timecourse, strength, location, etc Plasticity: changes in synaptic structure and function associated with development, aging, learning etc ↳ indirectly gated synapses W Neuron structure/polarity dendrites direction of flow cell body nucleus presynaptic postsynaptic axon hillock axon presynaptic synaptic terminals postsynaptic Synaptic Transmission 1. AP (action potential) arrives in presynaptic terminal Calcium movies neuon into presynaptic andfurn Voltage-gated Ca2+ channel AP important Ca2+ 3. Voltage-gated Ca2+ channels open Ca2+ presynaptic axon terminal 2. Presynaptic terminal depolarizes postsynaptic neuron 4. Ca2+ influx into presynaptic terminal + -+ + .e distri + + ↓ Open 5. Increased Ca2+ causes synaptic vesicles to fuse with presynaptic membrane. 6. Transmitter released by exocytosis and diffuses across synaptic cleft. bind to, and open ligand-gated ion channels. 7. Ions flow across membrane as dictated by their concentration gradients and depolarize (EPSP) or hyerpolarize (IPSP) postsynaptic cell [directly-gated]. 8. Transmitter removed and recycled or degraded. Ion channel closes, PSP ends ↳ Excitetury Synaptic Transmission Presynaptic neuron can be excitatory Releases excitatory neurotransmitter glutamate + + + - - - •Glutamate binds to receptor and opens ligand-gated Na+ channels ~brings a little closer to threshold •Na+ enters postsynaptic cell and results in small depolarization known as excitatory postsynaptic potential (EPSP). EPSPs are subthreshold. ↳ Makes a H more negative 0 Em -70 threshold Presynaptic neuron can be inhibitory Releases inhibitory neurotransmitter glycine or GABA + + - - - + Cl •Inhibitory transmitters (GABA, glycine) and opens ligand-gated Cl- channels bind to receptor •Cl- enters postsynaptic cell and results in small hyperpolarization known as inhibitory postsynaptic potential (IPSP) and prevent generation of APs. 0 Em -70 threshold * no refractory ↳ PSP period can more in Either direction 1 PSP gettis smaller smaller,smaller Pre-synaptic - , smartpoltication ⑭ brained dendrit Si dendrite axon Voltage- Gate Nat ↳ need channels to get to threshold . 69 # ↓ addition PSPs summate. le ing pre-synaptic These terminal & postsynaptic tw ear pends on -dage * Pre-synaptic ! a l . Excitetory terminal peacee - yus I ne ↓ An Er Em is Great - sam apart summation no C · ↳ 2 subthreshold's combined > Recording of reach - - membrane potential & terminals to up in to add time reach AP Summation of EPSP and IPSPS PSPs summate. •Temporal Summation: when PSPs from single presynaptic axon overlap in time they add together. In this way EPSPs, that alone are too small to initiate an AP, can sum together to bring the membrane to threshold and initiate and trigger an action potential •Spatial Summation: process by which PSPs generated in different regions of the postsynaptic neuron are added together. Summation of EPSPs from different regions that alone are too small to initiate an AP can depolarize the membrane to threshold and trigger an AP. •NOTE: both processes, spatial and temporal summation, occur simultaneously in the brain. For spatial summation to occur, the PSPs from different regions must also overlap in time. •Excitatory and Inhibitory signals are integrated into a single response by the postsynaptic neuron. Synaptic Integration. EPSP/IPSP in decrease magnitude as it travels > especially reaches Axon when Helic every Small by time reaches IDSD' summation and WhereEPSP an ollur axon ⑳ ? Value ↳lots of Synaptic Input in ALL Newors does much of after EPSP : What not lose as charge •Neurons receive on average inputs from 10,000-40,000 other neurons. •Integration: process of summing together all the inputs into a pattern of action potential output in the postsynaptic cell. it is postsynaptic potentio axon hiliz trong& ↳ hiliz PSPs summate. Integration problem: a neuron sits at -70 mV and has a threshold of -50 mV. It then simultaneously receives 10 IPSPs of 0.5 mV each and 20 EPSPs of 1 mV each. Does the cell fire an AP? ↳ AP would not occur - 15 Mr sum - -> - ~) not enough to fire Ap in this Situation PSPs summate. Integration problem: a neuron sits at -70 mV and has a threshold of -50 mV. It then simultaneously receives 10 IPSPs of 0.5 mV each and 20 EPSPs of 1 mV each. Does the cell fire an AP? Membrane Potential Effect of 10 IPSPs and 20 EPSPs all together -50mV -70mV Effect of 20 EPSPs only (1 mV each) Effect of 10 IPSPs only (0.5 mV each) Synaptic integration increases complexity of behaviour. * Reaction to same different dependant stimulus on may setting/contex Inhibitory input from cortex xcitting inpar from Comparison of PSPs and APs. Property PSP Amplitude graded (depol or hyperpol) all-or-none Duration msec - sec msec most occur on dendrites and soma initiated at axon hillock: transmit to synaptic terminal passive (over short distances) active (long distance transmission) change potential of post synaptic neuron, moving it closer (EPSP) or further (IPSP) from threshold. APs are triggered when summation depolarizes the membrane to threshold. If summation at axon hillock decides that the neuron will fire an AP, the AP is conducted to the terminal where it causes a PSP in the postsynaptic neuron. Location Conduction Function AP Neuron structure/polarity Material to be covered: • • • GOAL: obtain a mechanistic understanding of a simple reflex behaviour. NERVE • • • • • Components of the nervous system, neuronal structure. Membrane structure of a neuron, pumps, channels, resting membrane potential. How an action potential is generated. How an action potential is transmitted. How the action potential travels between neurons. MUSCLE • • SYNAPSE How the signal travels from neuron to muscle. How the electrical signal is converted into a mechanical movement (i.e. muscle contraction). Lecture Objectives: • Understand how efferent neurons connect to, and generate contraction of muscle. • Be able to identify the components and mechanisms involved in muscle contractions (i.e. cross-bridge cycling) • Be able to identify the anatomical and functional differences between red and white muscle fibres. 3 Types of Muscle: Smooth Muscle: Found in the walls of the hollow organs of the body. Its contraction reduces the size of the structures. regulates the flow of blood through the arteries. moves food through the GI tract. expels urine from the bladder. regulates the flow of air through the lungs. Contraction of smooth muscle is generally not under voluntary control. Cardiac Muscle: Striated muscle found in the walls of the heart. Propels blood into the heart and through the blood vessels of the circulatory system Not under voluntary control! Skeletal Muscle: Muscle attached to the skeleton. Also called striated muscle. Contraction of skeletal muscle is under voluntary control. Motor unit: motoneuron, its axon, and all the muscle fibers it activates. It is the functional unit of the motor system - it represents the smallest increment in force that can be generated Differences between synaptic transmission at neuromuscular junction and a central synapse: i. one AP in motoneuron generates one AP in muscle cell (summation required in CNS) ii. Each muscle fiber (cell) is only innervated by one presynaptic axon iii. no inhibitory transmitters released at N-M junction (how then is a muscle action stopped?) EXCITATION CONTRACTION COUPLING: How is the electrical signal of the AP converted to mechanical force? 87 Excitation-contraction Coupling DHP receptor Ryanodine receptor 1 Muscle action potential propagated Contraction Transverse tubule Sarcoplasmic Lateral sac reticulum Ca2+ Sarcoplasmic reticulum T tubule Cytosol 2+ released Ca 2 from lateral sac DHP: dihydropyridine receptor Ca2+ Ca2+ ATP ADP Relaxation Muscle plasma membrane FIRST: Muscle action potential propogated through t-tubule system, causing release of calcium from sarcoplasmic reticulum into cytosol. Coupling is through DHP and ryanodine receptor. Then: 3. Pumping Ca2+ back into the sarcoplasmic reticulum 110