Introductory Physiology Lectures – S1A PDF

1 Introductory Physiology Lectures – S1A Foundations for understanding Systems & Integrated Physiology 1 Overview and Scientific Process Think! How the body 2-3 Systems, tissues, cells (gen...

1 Introductory Physiology Lectures – S1A Foundations for understanding Systems & Integrated Physiology 1 Overview and Scientific Process Think! How the body 2-3 Systems, tissues, cells (genes), body water is organised 4-5 Transport processes (across cell membranes) Basis for Understanding 6 Bio-electric potentials (and ion distribution) System Function - 8 Nerve Physiology Just 1 of 11 systems 9+ Muscle plus the other 9 systems and integration The other 10 Dr Ruane-O’Hora, (Dr Markos, Dr Healy) systems 2 Introductory Physiology Lectures – S1A Foundations for understanding Systems & Integrated Physiology 1 Overview and Scientific Process Think! How the body 2-3 Systems, tissues, cells (genes), body water is organised 4-5 Transport processes (across cell membranes) Basis for Understanding 6 Bio-electric potentials (and ion distribution) System Function - 8 Nerve Physiology Just 1 of 11 systems 9+ Muscle plus the other 9 systems and integration The other 10 Dr Ruane-O’Hora, (Dr Markos, Dr Healy) systems 3 Lecture Learning Outcomes Give a simple overview of nervous system Describe role of sensory cells and graded potentials Describe role of neurotransmitters and synapses Role of graded potentials in nerve cell body Action potentials in nerve cell axons Explain why APs propogate in one direction / role of neuroglia More synapses and neuronal circuits 4 Nervous System: Overview Muscle stretch receptors PL2010 Muscle function PL2010 DECISION? Cardiac function PL2017 Other AN/PL3 5 Nervous System: Overview Muscle stretch receptors Sensing external environment Sensing internal environment Muscle function DECISION? Cardiac and GIT Other 6 Nervous System: Overview Muscle stretch receptors Sensing external environment Sensing internal environment Muscle function DECISION? Cardiac and GIT Other Nose Experiment! 7 Nervous System – three types of neuron But how are nerve impulses generated and propagated? 8 Neurons and neuronal circuits: Overview Sensory cell neuron neuron 9 Neurons and neuronal circuits: Overview Virtually all sensory systems Sensory have a sensory cell type which cell neuron releases neurotransmitters when activated Sweet taste buds detect glucose and other molecules that bind to a “sweet” receptor neuron 10 Neurons and neuronal circuits: Overview Virtually all sensory systems Sensory have a sensory cell type which cell neuron releases neurotransmitters when activated Sweet taste buds detect glucose Sensory Cell and other molecules that bind to a “sweet” receptor Salt taste buds detect Na+ ions in saliva Visual receptors detect photons of light Stretch receptors detect change in muscle length neuron 11 Nerve Impulse Transmission The role of Ion Channels Sensory cells graded potentials – increase in stimulus on sensory cells increases the membrane potential information travels short distance by diffusion information transfer is quick (NT = neurotransmitter) 12 Nerve Impulse Transmission The role of Ion Channels Synapses release of neuro- transmitters (NTs) from pre-synaptic cell Sensory cell terminal NT travels short distance by diffusion information transfer is very quick NT binds to post- synaptic cell (NT = neurotransmitter) 13 Nerve Impulse Transmission The role of Ion Channels Sensory cells cell body of a nerve cell also acts as a sensory cell gathering info from dendrites graded potentials are also generated in the cell body of nerve cells (NT = neurotransmitter) 14 Nerve Impulse Transmission The role of Ion Channels Axons action potentials – information travels much longer distances in axons than across cell body or synapse very quickly up to ~100 metres/second (NT = neurotransmitter) 15 Nerve Impulse Transmission The role of Ion Channels Synapses release of neuro- transmitters (NTs) from pre-synaptic cell NT travels short distance by diffusion information transfer is very quick NT binds to post- synaptic cell What are the mechanisms? (NT = neurotransmitter) 16 But first a question… The “electrical” information in all nerve cells is the same… … so how does the brain tell the difference between two stimuli? 17 The sight of crisps...... generates APs in nerves connected to rod and cone cells in your retina They are exactly the same impulses in two different nerves, but your brain can tell the difference - how? Taste of crisps......generates APs in nerves connected to taste buds in your tongue  Brains view of the world 18 Taste: strong signal Sight: strong signal Nerve endings terminate in different regions of the brain, hence the brain “knows” from where the action potentials came https://www.nature.com/articles/nature18933 19 Lecture Learning Outcomes Give a simple overview of nervous system Describe role of sensory cells and graded potentials Describe role of neurotransmitters and synapses Role of graded potentials in nerve cell body Action potentials in nerve cell axons Explain why APs propogate in one direction / role of neuroglia More synapses and neuronal circuits 20 Lecture Learning Outcomes Give a simple overview of nervous system Describe role of sensory cells and graded potentials Describe role of neurotransmitters and synapses Role of graded potentials in nerve cell body Action potentials in nerve cell axons Explain why APs propogate in one direction / role of neuroglia More synapses and neuronal circuits 21 Sensory cell Synapse Sensory cell Axon Nerve terminals I Synapse Sensory cell Axon and Nerve terminals II (NT = neurotransmitter) 22 Sensory cell Synapse Sensory cell Sensory cell terminal Axon Nerve terminals I Synapse Sensory cell Axon and Nerve terminals II (NT = neurotransmitter) 23 Sensory cell Synapse Sensory cell Axon Nerve terminals I Synapse Sensory cell Axon and Nerve terminals II (NT = neurotransmitter) 24 Sensory cell Synapse Sensory cell Axon Nerve terminals I Synapse Sensory cell Axon and Nerve terminals II (NT = neurotransmitter) 25 Sensory cell Synapse Sensory cell Axon Nerve terminals I Synapse Sensory cell Axon and Nerve terminals II (NT = neurotransmitter) 26 Sensory cell Synapse Sensory cell Axon Nerve terminals I Synapse Sensory cell Axon and Nerve terminals II (NT = neurotransmitter) 27 Sensory cell Synapse Sensory cell Axon Nerve terminals I Synapse Sensory cell Axon and Nerve terminals II (NT = neurotransmitter) 28 Sensory cell Synapse Sensory cell Axon Nerve terminals I Synapse Sensory cell Axon and Nerve terminals II (NT = neurotransmitter) 29 Sensory cells upon stimulation, graded potentials result in graded release of neurotransmitters Synapses NTs released from pre-synaptic cell and diffuse short distance to post-synaptic cells Sensory cells NT receptors on cell body of nerve cell generate graded potentials at axon hillock Axons if threshold of -55 mv is NOT reached, nothing happens if threshold of -55mV is reached, a low frequency of action potentials are generated & propagated along the axon if threshold of -55mV is maintained, a high frequency of action potentials are generated & propagated along axon Nerve terminals I “arrival” of action potential triggers NT release and binds to other nerve cells – see later Nerve terminals II see other lectures in this module 30 Nerve Impulse Generation Activation of sensory cells via ion channels Na+ 1 2 Ca2+ 3 (NT = neurotransmitter) 31 Step 1: Activation of gated Na+ channels on surface of sensory cells causes rapid Na+ influx … Na+ Ligand Gated 2 Na+ mV Ca2+ Extracellular -70 Intracellular 3 A ligand (e.g. sugar, drug, hormone) binds to channel and causes the ligand-gated Na+ channel to open Na+ rushes into cell and membrane potential increases (rapidly) 32 Step 1: Activation of gated Na+ channels on surface of sensory cells causes rapid Na+ influx … Na+ Ligand Gated 2 Na+ mV Ca2+ Extracellular -70 Intracellular 3 A ligand (e.g. sugar, drug, hormone) binds to channel and causes the ligand-gated Na+ channel to open Na+ rushes into cell and membrane potential increases (rapidly) 33 Step 1: Activation of gated Na+ channels on surface of sensory cells causes rapid Na+ influx … … this generates a graded potential Ligand Gated Na+ 2 mV Ca2+ Extracellular -70 Intracellular Na+ 3 A ligand (e.g. sugar, drug, hormone) binds to channel and causes the ligand-gated Na+ channel to open Na+ rushes into cell and membrane potential increases (rapidly) 34 Step 2: Rapid influx of Na+ increases membrane potential & activates voltage-gated Ca2+ channel Voltage Gated Na+ 2 Ca2+ Ca2+ Extracellular Intracellular + + + + 3 An increase in resting membrane potential (see later for mechanism) opens voltage-gated Ca2+ channel Ca2+ rushes into cell and membrane potential increases (very rapidly) 35 Step 2: Rapid influx of Na+ increases membrane potential & activates voltage-gated Ca2+ channel Voltage Gated Na+ 2 Ca2+ Ca2+ Extracellular Intracellular + + + + 3 An increase in resting membrane potential (see later for mechanism) opens voltage gated Ca2+ channel Ca2+ rushes into cell and membrane potential increases (very rapidly) 36 Step 2: Rapid influx of Na+ increases membrane potential & activates voltage-gated Ca2+ channel Voltage Gated Na+ 2 Extracellular Ca2+ Intracellular + + + Ca2+ + 3 An increase in resting membrane potential (see later for mechanism) opens voltage gated Ca2+ channel Ca2+ rushes into cell and membrane potential increases (very rapidly) 37 Step 3: Rapid influx of Ca2+ diffuses across entire cell causes NT vesicles fuse to presynaptic membrane NT NT NT Na+ 2 Ca2+ Ca2+ Intracellular Ca2+ Extracellular 3 Ca2+ causes fusion of NT containing vesicles NT released into synapse (rapid) 38 Step 3: Rapid influx of Ca2+ diffuses across entire cell causes NT vesicles fuse to presynaptic membrane Na+ 2 NT Intracellular Ca2+ NT Ca2+ Ca2+ Extracellular NT 3 Ca2+ causes fusion of NT containing vesicles NT released into synapse (rapid) 39 Step 3: Rapid influx of Ca2+ diffuses across entire cell causes NT vesicles fuse to presynaptic membrane Na+ 2 Intracellular Ca2+ NT Ca2+ Ca2+ Extracellular NT NT 3 Ca2+ causes fusion of NT containing vesicles NT released into synapse (rapid) 40 Sensory cell convert stimulus into NT release Small A small stimulus stimulus generates a small graded potential … Na+ 2 -55 … and this triggers a small amount of Ca2+ mV NT release -70 Small graded 3 Small NT potentials release -55 -70 41 Sensory cell convert stimulus into NT release Large A large stimulus stimulus generates a large graded potential … Na+ 2 -55 … and this triggers Na+ a large amount of Na+ Ca2+ mV NT release Ca2+ -70 Ca2+ Large graded 3 Lots of NT potentials release -55 -70 42 Sensory cells upon stimulation, graded potentials result in graded release of neurotransmitters Synapses NTs released from pre-synaptic cell and diffuse short distance to post-synaptic cells Sensory cells NT receptors on cell body of nerve cell generate graded potentials at axon hillock Axons if threshold of -55 mv is NOT reached, nothing happens if threshold of -55mV is reached, a low frequency of action potentials are generated & propagated along the axon if threshold of -55mV is maintained, a high frequency of action potentials are generated & propagated along axon Nerve terminals I “arrival” of action potential triggers NT release and binds to other nerve cells – see later Nerve terminals II see other lectures in this module 43 Sensory cells upon stimulation, graded potentials result in graded release of neurotransmitters Synapses NTs released from pre-synaptic cell and diffuse short distance to post-synaptic cells Sensory cells NT receptors on cell body of nerve cell generate graded potentials at axon hillock Axons if threshold of -55 mv is NOT reached, nothing happens if threshold of -55mV is reached, a low frequency of action potentials are generated & propagated along the axon if threshold of -55mV is maintained, a high frequency of action potentials are generated & propagated along axon Nerve terminals I “arrival” of action potential triggers NT release and binds to other nerve cells – see later Nerve terminals II see other lectures in this module 44 NTs bind NT receptors on post-synaptic cell NT-Rs on nerves synapsed to sensory cells are ligand-gated Na+ channels +30 Na+ mV -70 mV -70 Voltage-gated Na+ and K+ channels in axon 45 NTs bind NT receptors on post-synaptic cell Na+ influx can raise membrane potential at axon hillock to threshold +30 Na+ mV -70 mV -70 46 NTs bind NT receptors on post-synaptic cell Na+ influx can raise membrane potential at axon hillock to threshold +30 mV -70 mV -70 Na+ Na+ 47 NTs bind NT receptors on post-synaptic cell Na+ influx can raise membrane potential at axon hillock to threshold +30 mV -60 mV -70 Na+ Na+ Na+ Na+ Na+ Na+ Na+ 48 At -55 mV a nerve impulse is sent along the axon… … but what is a nerve impulse, how fast is it, why does it go in one direction? +30 mV -55 mV -70 Na+ Na+ Na+ Na+ Na+ Na+ Na + Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ 49 Nerve impulses - a few thoughts 1 metre Toe Spinal 1 /100 second Cord = 100 ms-1 = 100 m x 3,600 s = 360,000 m in an hour… 50 Nerve impulses - a few thoughts 1 metre Toe Spinal 1 /100 second Cord = 100 ms-1 Copper wire = 1,000,000,000 Km/h 3 x 106 slower Nerve Impulse = 360 Km/h 4 x 1010 faster Diffusion = 0.000 000 008 Km/h What is the mechanism? 51 Glu 0 24 48 Time (mSec) Nothing – resting membrane potential of -70mV “Nothing!” 52 Glu Glu 0 24 48 Time (mSec) Low frequency of action potentials (APs) “Not enough!” 53 Glu Glu Glu Glu 0 24 48 Time (mSec) Medium frequency of action potentials (APs) “Just right!” 54 Glu Glu Glu Glu Glu Glu Glu 0 24 48 Time (mSec) High frequency of action potentials (APs) “Too sweet!” 55 Two questions… Q1. What are action potentials ? A1. Small identical electrical changes in individual parts of a neuron… Q2. But what’s actually happening? 56 Lecture Learning Outcomes Give a simple overview of nervous system Describe role of sensory cells and graded potentials Describe role of neurotransmitters and synapses Role of graded potentials in nerve cell body Action potentials in nerve cell axons Explain why APs propogate in one direction / role of neuroglia More synapses and neuronal circuits 57 Action Potentials Sensory cell Synapse Sensory cell Axon Nerve terminals I Synapse Sensory cell Axon and Nerve terminals II (NT = neurotransmitter) 58 Diffusion times of ions to acheive 99% equilibrium Distance (µm) Time (s) Nerve 0.1 0.000 000 5 synapse Synaptic transmission can work by diffusion Typical 10 0.05 Cell Graded potentials can work by diffusion Longest 1,000,000 (1 metre) 500,000,000 (15 years) Nerve But how can nerve impulses work by diffusion? 59 Graded potentials +30 Na+ mV -70 mV -70 Voltage-gated Na+ and K+ channels in axon 60 Graded potentials +30 Na+ mV -70 mV -70 61 Graded potentials +30 mV -70 mV -70 Na+ Na+ 62 Graded potentials +30 mV -60 mV -70 Na+ Na+ Na+ Na + Na+ Na+ Na+ 63 Decision Point +30 mV -55 mV -70 Na+ Na+ Na+ Na+ Na+ Na+ Na + Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ 64 Action potentials Very rapid changes in membrane potential – why and how? +30 mV -70 Na+ Na+ Na+ Na+ Na+ Na + Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Voltage-gated Na+ and K+ channels in axon  Resting membrane potential (RMP) 65 Inside is negative relative to outside –70 mV Na+ K+  Graded potentials 66... increases membrane potential to -55 mV Na+ K+  At -55 mV Na+ channels open 67... increases membrane potential to +30 mV Na+ K+ Influx of Na+ is extremely rapid because... Na+ gradient is large and Electrical gradient is large  Na+ channels close at peak of AP 68 Maximum Potential +30mV Na+ K+  K+ channels open at +30 mV 69... decreases membrane potential to –90 mV Na+ K+ Efflux of K+ is extremely rapid because... K+ gradient is large and Electrical gradient is large  Na+ / K+ pump helps resets RMP 70 Membrane Potential –70 mV Na+ K+ Na+ / K+ Pump 71 Lecture 7 Action potentials in nerve cell axons Explain why APs propagate in one direction Role of neuroglia / myelin sheath Specialised sensory cells Describe mechanism of synaptic transmission Role of Synapses in Neuronal Circuits Local anaesthetics versus neurotoxins – mechanism of action 72 Introductory Physiology Lectures – S1A Foundations for understanding Systems & Integrated Physiology Reminders Overview and Scientific Process Think! No class on Tuesday 8th October How the body Class isSystems, tissues, on Thursday cells (genes), body water as usual is organised Transport processes (across cell membranes) Basis for Understanding Bio-electric potentials (and ion distribution) System Function Nerve Physiology Just 1 of 11 systems Muscle plus the other 9 systems and integration The other 10 Dr Ruane-O’Hora, (Dr Markos, Dr Healy) systems