ANIM 1005 Veterinary Anatomy & Physiology Lecture 2 PDF

2024-09-25 ANIM 1005 Veterinary Anatomy and Physiology Dr. Pauline Smith Contact: [email protected] Rm 00600 1 1  2024-0...

2024-09-25 ANIM 1005 Veterinary Anatomy and Physiology Dr. Pauline Smith Contact: [email protected] Rm 00600 1 1  2024-09-25 Outline for today’s class: ▪ The action potential ▪ Neuromuscular Junction Test # 3 Tuesday Oct 15th: Nervous System and Muscular Contraction 75 min (12:30-1:45), Format: true/False Multiple choice Short Answer 2 2  2024-09-25 The Action Potential 3 3  2024-09-25 The Action Potential In response to the appropriate stimulus, the cell membrane goes through a sequence of electrical events Each neuron receives an impulse and must pass it on to the next neuron and make sure the correct impulse continues on its path. Through a chain of chemical events, the dendrites pick up an impulse which is shuttled through the axon and transmitted to the next neuron. The entire impulse passes through a neuron in about 7 ms (faster than a lightning strike!) 4 4  2024-09-25 Resting Membrane Potential (RMP) RMP = electrical voltage that can be measured (mV) across the cell membrane ▪ Usually ranges between -40mV to -90mV ▪ Why negative? due to differential separation of charged ions (Na+ and K +) across the cell membrane and the membranes differential permeability to these ions as they attempt to move down their concentration gradient. ↓ ↑ +ve charge outside ↑-ve charge inside 5 5  2024-09-25 Ionic Distribution Across the Cell Membrane Na+ Cl- K+ Na+ Cl- Na+ Na+ Cl- Cl- Na+ Na+ K+ Na+ K+ K+ K+ K+ Na+ K+ Na+ K+ Cl- K+ Na+ Cl- Cl- K+ K+ ↑Protein Na+ Cl- K+ K+ Na+ K+ Cl- Cl- K+ Cl- Na+ Na+ 6 6  2024-09-25 Determinants of RMP 3 major factors that determine (maintain) the RMP: 1) Differential permeability of the membrane 2) The Na+/K+ pump 3) Movement of ions toward a dynamic equilibrium 7 7  2024-09-25 Determinants of RMP (cont.) 1) Differential permeability of the membrane H2O soluble ions do not diffuse through the lipid bilayer, they move through ion channels permeability to a particular ion is determined by the number of open channels 8 8  2024-09-25 Determinants of RMP (cont.) 2) The Na+/K+ pump energy dependent pump that moves Na+ (3) out of the cell and K + (2) into the cell against their concentration gradient Na+/K+ Pump ATP is derived from intracellular glucose and O2 which the neuron does not store. Therefore, anything that deprives the NS of glucose or O2 can cause serious neurological defects! 9 9  2024-09-25 Determinants of RMP (cont.) 3) Movement of ions toward a dynamic equilibrium - 2 driving forces: 1) concentration gradient (chemical driving force) 2) electrical gradient (electrical driving force) Chemical Electrical gradient gradient These opposing gradients + - + - produce a dynamic equilibrium + - - + (due to differences in distribution of ions and a charge imbalance). K+ gradient K+ gradient + - - + This unequal distribution of + - + - charge at dynamic equilibrium K+ moves down K+ moves along its produces a voltage across the [ ] gradient out electrical gradient membrane of the cell into the cell 10 10  2024-09-25 The Action Potential Action Potentials: Large rapid changes in MP due to the opening of voltage gated ion channels RMP can be altered by chemical signals (neurotransmitter) from a presynaptic neuron. Neurotransmitters bind with receptors on the postsynaptic membrane → ion channels open → change in MP of the postsynaptic cell. 11 11  2024-09-25 The Action Potential Resting Membrane Potential 12 12  2024-09-25 Action Potential Terms 1) Depolarization: The membrane potential becomes more positive 2) Hyperpolarization: The membrane potential becomes more negative 3) Repolarization: The membrane returns to resting potential after having been depolarized 4)Threshold: The membrane potential that must be attained for an AP to be generated (stimulus of sufficient strength to cause the opening of enough Na+ channels to achieve a complete depolarization) All-or-none principle: if initial stimulus was strong enough to reach threshold and cause a depolarization, the AP will be conducted along the entire neuron with equal strength 13 13  2024-09-25 The Action Potential: Events 1) Initiation: Stimulus (other neuron or external (ie heat , touch, etc.) of sufficient strength to generate AP) 2) Depolarization: Opening of Na+ channels and sufficient Na+ influx into the cell 3) Repolarization: Change of cells ‘charge’ back towards –ve potential 4) Refractory period: Period of time when normal stimulus will not generate a 2nd AP 14 14  2024-09-25 The Action Potential: Events (Overview) 15 15  2024-09-25 The Action Potential: Depolarization 1) Cell at rest (Resting Membrane Potential) 2) Stimulus occurs at neuron (more to follow!) 3) Membrane depolarizes to threshold, Na+ channel opens and Na+ enters the cell due to a) concentration gradient b) net -ve charge inside the cell 4) Na+ channel opening and rapid influx of Na+ causes membrane potential to go from –ve to +ve This large change in electrical charge is called the action potential. 16 16  2024-09-25 The Action Potential: Repolarization 5) Na+ channels shut, K+ channels open 6) K+ flows out of the cell due to Repolarization: cell’s charge a) concentration and back toward -ve RMP b) electrochemical gradient 7) K+ channels stay open allowing more K+ to exit the cell and the cell to hyperpolarize 8) Voltage-gated K+ channels close 9) Resting ionic distribution (and RMP) reestablished What’s the difference between Repolarization and RMP? - location of Na+ & K+ are reversed (rectified Na+/K+ pump) 17 17  2024-09-25 The Action Potential: Refractory Period Refractory period: the time during the AP when a 2nd stimulus of normal strength is incapable of generating a 2nd AP Absolute Refractory Period: time when NO stimulus, regardless of size, can cause the cell to generate a 2nd AP (period of Na+ influx and early K+ outflow). Relative Refractory Period: time toward the end of the refractory period when a normal stimulus can not cause a depolarization, but a large stimulus may cause a depolarization 18 18  2024-09-25 Postsynaptic Potentials Postsynaptic Potential: change in voltage in the postsynaptic membrane - change be toward a more –ve or +ve potential Excitatory postsynaptic potential (EPSP): chemical synaptic transmission leads to a more positive MP in the postsynaptic membrane - brings the MP toward threshold, ↑ chance of an AP 19 19  2024-09-25 Postsynaptic Potentials (cont.) Inhibitory postsynaptic potential (IPSP): chemical synaptic transmission leads to a more negative MP in the postsynaptic membrane - brings the MP away from threshold, ↓ chance of an AP 20 20  2024-09-25 Summation If a postsynaptic neuron is receiving both IPSPs and EPSPs how is it possible to generate an action potential? Answer: Summation Summation: process by which all inputs are ‘added up’ by the soma Types: 1) Temporal Summation of input from a single synapse over time 2) Spatial Summation of inputs from multiple synapses All at the same time, can produce action potentials 21 21  2024-09-25 The Action Potential: Conduction Wave of depolarization: stimulus causing threshold to be reached at one area in neuron causes adjacent Na+ channels to be opened, causing a depolarization which continues over the entire neuron 22 22  2024-09-25 Conduction of Action Potentials 23 23  2024-09-25 Saltatory conduction action potential is conducted along the length of the axon by ‘jumping’ from one Node of Ranvier to the next rapid means of conduction It is this rapid conduction that makes process such as vision and fine motor control possible in larger species 24 24  2024-09-25 The Synapse 25 25  2024-09-25 Cell to Cell Conduction: the Synapse Once the AP reaches the end of the axon, the information must be conveyed to the next neuron, or cells of the target organ or tissue Synaptic transmission: perpetuation of the impulse from the neuron to the next cell. Types of Synapses: a) Electrical synapses: gap junctions very fast conduction; (eg cardiac muscle) b) Chemical synapses: involves the synthesis and release of neurotransmitters 26 26  2024-09-25 The Chemical Synapse Neurotransmitters are released from the axon terminal of the presynaptic membrane into the synapse where they combine with receptors on the postsynaptic membrane Presynaptic terminal Synaptic cleft Postsynaptic cell 27 27  2024-09-25 Neurotransmitter Release Presynaptic neuron Synapse Postsynaptic neuron 28 28  2024-09-25 Postsynaptic Receptor: Classification 1) Transmitter Specific a) Excitatory: Causes an influx of Na+ causing the postsynaptic membrane to depolarize If postsynaptic membrane is stimulated by enough excitatory neurotransmitter, the membrane will depolarize to threshold and an action potential will occur b) Inhibitory: Causes Cl- and K+ channels to open → influx of Cl- and efflux of K+ causing the postsynaptic membrane hyperpolarize Postsynaptic membrane does not depolarize to threshold with a normal stimulus Neurotransmitters can usually be classified according to their effect on the postsynaptic membrane, however some neurotransmitters are excitatory or inhibitory depending on site and receptor activated. 29 29  2024-09-25 Postsynaptic Receptors: Classification (cont) 2) Response Specific a) Ionotrophic: Direct effect on ion channels → change in membrane potential Most neurotransmitters function by changing the configuration of voltage gated channels, altering membrane permeability b) Metabotrophic: Interaction activates a second messenger system within the postsynaptic neuron leads to a variety of postsynaptic responses ie) cAMP: intracellular messenger that can lead to short-term effects (the opening of ionic gates) or long-term effects on the postsynaptic neuron (alter gene expression, play a role in learning and memory) 30 30  2024-09-25 Neurotransmitters: Classification 1) Classical Neurotransmitters: small (low molecular weight) rapid-acting molecules a) Amines (acetylcholine, serotonin, histamine) i) Acetylcholine Excitatory: synapse between somatic motor neurons and the muscles they supply to cause a muscle contraction Inhibitory: synapse at the heart where it acts to decrease HR b) Catecholamines i) Norepinephrine arousal and ‘fight or flight’ reactions of the sympathetic NS ii) Epinephrine acts as a hormone in ‘fight or flight’ reactions of the SNS iii) Dopamine involved in autonomic functions and muscle control 31 31  2024-09-25 Neurotransmitters: Classification (cont) 1) Classical Neurotransmitters (cont.) c) Amino Acids (glutamate, gamma-aminobutyric acid (GABA), glycine) i) Glutamate: excitatory neurotransmitter ii) GABA and iii) glycine : inhibitory neurotransmitter that act to decrease activity in the brain (target of some tranquilizers) 2) Neuropeptides: large (higher molecular weight), slow-acting ie) angiotensin II, cholecyctokinin, α MSH, somatostatin, substance P, vasopressin, opioids (Leu- and Met- enkaphalin, β endorphan) 3) Novel (non-traditional) Transmitters: very lipophilic i) Gases: NO and CO2 ii) Purines: Adenosine and Adenosine triphosphate (ATP) 32 32  2024-09-25 Stopping & Recycling Neurotransmitters 1) Re-uptake 2) Enzyme degradation 3) Diffuse away 4 4) Receptor/ligand complex internalization (postsynaptic cell) 33 33  2024-09-25 Neuromuscular Junction 34 34  2024-09-25 Neuromuscular Junction Synapse between a motor neuron and a skeletal muscle cell Specialized for one way communication 35 35  2024-09-25 Recall: Muscle Fibers* Figure 6-2 Several muscle fibers(cells) make up a muscle Span the distance between tendons Diameter: 5-100µm Contain several nuclei/muscle fiber, lots of mitochondria Surrounded by the sarcolemma Innervated by 1 motor neuron – neuromuscular junction is at center of muscle fiber Each fiber is made up of myofibrils 36 36  2024-09-25 Neuromuscular Junction: Anatomy Cell body in CNS (brain stem or spinal cord) Axon travels within peripheral nerves to the muscle (may innervate several muscle fibers) Individual muscle fibers receive input from only Figure 5-1 1 motor neuron 37 37  2024-09-25 Neuromuscular Junction: Anatomy Synaptic vesicles contain acetylcholine (ACh) Junctional folds of skeletal muscle cell ↑ surface area for Figure 5-1 ACh receptors 38 38  2024-09-25 Neuromuscular Junction: Anatomy Site where synaptic vesicles will release ACh (50nm) Figure 5-2 39 39  2024-09-25 Synaptic Inactivation of ACh ACh is broken down in the synaptic cleft by acetylcholinesterase (AChE) Figure 5-3 40 40  2024-09-25 Lecture 3 (Monday) Oct 7 41 41  2024-09-25 Outline for today’s class: ▪ The Physiology of Muscle ▪ Skeletal Muscle Receptor Organs Test # 3 Tuesday Oct 15th: Nervous System and Muscular Contraction 75 min (12:30-1:45), Format: true/False Multiple choice Short Answer 42 42  2024-09-25 The Physiology of Muscle 3 types of muscle 1) Cardiac (heart) 2) Smooth (internal organs) Cardiac 3) Skeletal ("voluntary“) Attach to bone Move appendages Smooth Support body Antagonistic pairs Flexors Skeletal Extensors 43 43  2024-09-25 Movement All movement is the result of contraction of skeletal muscle across a moveable joint Muscle: spans a joint Tendons: fibrous connective tissue that attaches ‘belly’ muscle to bone Consists of 2 or more attachment sites Origin: stable site of muscle attachment that does not move during contraction Insertion: site of muscle attachment that moves during contraction Skeletal Muscle contracts = movement of limb Figure 6-1 44 44  2024-09-25 Skeletal Muscle Contraction: Overview Excitation-Contraction Coupling: combination of electrical and mechanical events 45 45  2024-09-25 Skeletal Muscle Contraction: Overview 46 46  2024-09-25 Levels of Organization of Skeletal Muscle Figure 6-2 47 47  2024-09-25 Myofibrils MYOFIBRIL Several hundred myofibrils, arranged in parallel, make up a muscle fiber - made up of linear, repeating sarcomeres (tens of thousands sarcomeres/ Figure 6-2 SARCOMERE muscle fiber) 48 48  2024-09-25 Sarcomere Contains 4 proteins: actin, tropomyosin, troponin, myosin Actin filaments: thin protein filaments attached to the Z disks which extend towards the center of the sarcomere Actin filament is composed of 2 intertwined strands of actin protein and 2 strands of tropomyosin protein Tropomyosin: elongated molecule that wraps around actin, blocking myosin/actin interactions Z disc 49 49  2024-09-25 Sarcomere (cont) Contains 4 proteins: actin, tropomyosin, troponin, myosin Troponin: located intermittently along actin filaments - can bind tropomysoin/actin - a high affinity for Ca2+ in non-stimulated state: binds to tropomyosin, blocking myosin attachment site in stimulated state: Ca2+ interaction with troponin shifts troponin which unblocks myosin attachment site Z disc 50 50  2024-09-25 Sarcomere (cont) Contains 4 proteins: actin, tropomyosin, troponin, myosin Myosin protein is suspended between and parallel to the actin filaments 2 heavy chains coil to form: 1) a head: bind ATP and actin ~ 500 join forming crossbridges that interact with actin to shorten the sarcomere 2) a tail: points toward center of the sarcomere Bundles of myosin form thick filament 51 51  2024-09-25 Sarcoplasmic Reticulum - stores and segregates Ca2+ when muscle is relaxed (actin) (myosin) 52 52  2024-09-25 Transverse Tubules (T tubules) Transverse the diameter of the muscle fiber An action potential generated in the sarcolemma at the neuromuscular junction (at the center of the muscle fiber) spreads in both directions along the length of the muscle fiber to the interior of the muscle via the T tubules Figure 6-3 53 53  2024-09-25 Excitation/Contraction Coupling The physiological process of converting an electrical stimulus to a mechanical response (action potential in the skeletal muscle cell is what triggers muscle contraction). Requires Ca2+ (but not for neurotransmitter release!) An action potential generated in the sarcolemma at the neuromuscular junction at the center of the muscle fiber spreads in both directions along the length of the muscle fiber to the interior of the muscle via the T tubules 54 54  2024-09-25 Excitation/Contraction Coupling (cont) ↑ Ca2+ in sarcoplasm (muscle cell cytoplasm) required for muscle contraction At rest: Ca2+ in sarcoplasm is pumped into and stored in SR→ too low Ca2+ in sarcoplasm to trigger contraction When AP and depolarization arrives at junction between T- tubules and SR → release of Ca2+ from SR → Ca2+ flows down concentration gradient into sarcoplasm → contraction When depolarization ends, Ca2+ in sarcoplasm is pumped back to SR → relaxation 55 55  2024-09-25 Sliding Filament Theory* In the presence of Ca2+ and ATP, actin filaments are pulled along myosin filaments by repetitive movement of the myosin head molecules → sarcomere shortens 56 56  2024-09-25 Sliding Filament Theory: Role of Ca2+ Tropomyosin: blocks myosin/actin interactions Troponin: binds tropomysoin/actin in absense of Ca2+, blocking the myosin attachment site Figure 1-5 57 57  2024-09-25 Sliding Filament Theory: Role of Ca2+ In presence of ↑Ca2+, Ca2+ binds to site in troponin → allosteric change in troponin → unblocking of myosin attachment site - myosin heads then bind with myosin binding sites and alternately relax and flex and move along the actin 58 58  2024-09-25 Skeletal Muscle Contraction: Overview Excitation-Contraction Coupling: combination of electrical and mechanical events 59 59  2024-09-25 Skeletal Muscle Contraction: Overview 60 60  2024-09-25 Regulation of Muscle Contraction Relaxation Ca 2+ pumped back into SR (by Ca2+-ATPase) → ↓ intracellular Ca2+ → removing Ca 2+ from troponin, allows tropomyosin to block myosin attachment site Acetylcholinesterase = deactivates ACh at neuromuscular junction When actin/myosin uncouple, muscle is pulled back to original length by elastic components of the sarcomere 61 61  2024-09-25 Skeletal Muscle Receptor Organs Receptors: monitor changes in muscle length and tension Types: 1) muscle spindles (monitor muscle length) 2) Golgi tendon organs (monitor muscle tension) Information received at receptors is used in 2 ways: 1) information regarding muscle length and tension is sent to motor areas of the brain 2) control muscle length and tension via negative feedback by means of local spinal reflexes 62 62  2024-09-25 Skeletal Muscle Receptor Organs (cont.) 1) Muscle Spindles: consist of A) Extrafusal fibres cause the physical shortening of the muscle (regular contractile fibres) innervated by α motor neurons (efferent neuron from CNS) B) Intrafusal fibres within (and parallel to) extrafusal fibres myofibrils limited to ends (no myofibrils in central portion) innervated by γ motor neurons (efferent neuron from CNS) form part of the sensory apparatus: wrapped in sensory receptors that detect changes in length during stretching 63 63  2024-09-25 Muscle Spindle Stretch Reflex 64 64  2024-09-25 Skeletal Muscle Receptor Organs (cont.) 2) Golgi Tendon Organs (GTOs): located in tendons at the end of muscle the muscle Sensory sense changes in tension of the neuron tendon produced by muscle contraction and sends this information to the CNS 65 65  2024-09-25 Skeletal Muscle Receptor Organs (cont.) 2) Golgi Tendon Organs (GTOs): How do they work? muscles contract → tendons are pulled,→ collagen fibers are stretched → GTOs fire → causes inhibition of α motor neurons of same muscle Result: slows/halts contraction of muscle as force increases Prevents excessive contraction and brings about a relaxation preventing damage 66 66