Mammalian Physiology

Types of Tissue

  • Four primary types of tissue: epithelial, connective, muscle, and nervous.

    • Epithelial Tissue: Non-excitable, incapable of conducting electrical signals.

    • Connective Tissue: Non-excitable, incapable of conducting electrical signals.

    • Muscle Tissue: Excitable, capable of conducting electrical signals.

    • Nervous Tissue: Excitable, capable of conducting electrical signals.

Nervous System Overview

  • The nervous system coordinates and controls other systems in the body.

  • Divided into three physiological divisions:

    • Sensory Division: Detects environmental challenges such as light, heat, glucose, and pH.

    • Integrative Division: Decides responses to environmental challenges.

    • Motor Division: Responds to environmental challenges (e.g., muscle contraction or relaxation).

Reflex Arc

  • A reflex arc includes all three divisions of the nervous system.

  • Example: Patellar Reflex (Knee Jerk Reflex):

    • Patellar tendon is tapped with a mallet, stimulating a sensory receptor.

    • Signal travels via a sensory nerve to the spinal cord, synapsing with an integrative neuron.

    • Integrative neuron synapses with a motor nerve, sending a signal to the quadricep muscle to contract, causing the leg to jerk.

    • See Figure 54-5 in the textbook for reference.

Motor Division Responses

  • Two mechanisms of response in the motor division:

    • Somatic Motor Branch: Stimulates skeletal muscles (always excited, contracts by shortening).

    • Autonomic Motor Branch: Stimulates smooth and cardiac muscles (can be excited or inhibited, performs work through various mechanisms).

Branches of Autonomic Motor System

  • Divided into two independent branches that create opposite responses:

    • Sympathetic Branch:

    • Controls smooth and cardiac muscle during emergencies (e.g., increases heart/breathing rates, decreases stomach contractions).

    • Parasympathetic Branch:

    • Controls smooth and cardiac muscle during vegetative (rest and digest) activities (e.g., decreases heart/breathing rates, increases stomach contractions).

Cell Communication

  • Cell to cell communication occurs through:

    • Chemical Transmission (between cells).

    • Electrical Transmission (within cells).

Integral Membrane Proteins in Neurons

  • Three key types for signal transmission:

    • Receptors: Located in the receptor zone, bind neurotransmitters.

    • Ion Gates: Present in receptor, conduction, and neurotransmission zones; specific to particular ions; typically closed until stimulated; allow ions to diffuse through when open via facilitated diffusion.

    • Ion Pumps: Found in receptor, conduction, and neurotransmission zones; actively transport ions against gradients; includes Sodium-Potassium and Calcium pumps, establishing ion gradients.

Resting Membrane Potential

  • The membrane potential at rest is approximately -70 mV.

  • Influenced by:

    • Large anions trapped inside the cell.

    • Potassium ions (K+) diffusing out slowly.

    • Accumulation of positive charges outside and negative charges inside creates a slight negative charge inside the cell.

Nernst Potential

  • The potential that would exist if only one type of ion could diffuse freely.

  • Affected by both chemical and electrical gradients.

  • At rest, Na+ has a strong tendency to enter the cell while K+ has a weak tendency to leave the cell; both cannot move effectively with gates closed.

Ion Gates

  • Chemically-Regulated Ion Gates: Found in the reception zone; open when neurotransmitters bind to receptors; include Na+, K+, Cl- gates.

  • Voltage-Regulated Ion Gates: Found in conduction and neurotransmission zones; open due to electrical changes; include Na+, K+, Ca++ gates.

Changes in Membrane Potential

  • Five types of electrical changes in excitable cells:

    1. Action Potential:

    • Occurs in the conduction zone of all neurons and muscles.

    • Follows the all-or-none principle (non-graded).

    • Self-propagating; requires voltage-regulated ion gates and an upstream electrical stimulus.

    • Phases:

      • Depolarization: Influx of Na+ through voltage-regulated Na+ gates.

      • Repolarization: Efflux of K+ through voltage-regulated K+ gates.

      • Sequential opening of Na+/K+ gates.

    1. Excitatory Post Synaptic Potential (EPSP):

    • Source of upstream stimulus for action potential.

    • Occurs in integrative and somatic motor neuromuscular synapses.

    • Graded, not propagated (local).

    • Opens chemically-regulated Na+/K+ gates due to neurotransmitter binding. Threshold at axon hillock required for action potential.

    1. Inhibitory Post Synaptic Potential (IPSP):

    • Occurs in integrative neuro-neuronal and neuromuscular synapses in autonomic pathways.

    • Graded, but nearly always sufficient to reach threshold; not propagated (local).

    • Opens either chemically-regulated K+ gates (efflux) or Cl- gates (influx), making the membrane more negative, preventing action potential.

    1. End Plate Potential (EPP):

    • Found in neuromuscular synapses in somatic motor pathways.

    • Graded but typically sufficient to reach threshold; not propagated.

    • Similar to EPSP but summation is not typically required.

    1. Generator Potential (GP):

    • Found in the reception zone of sensory receptors and sensory neuron synapses.

    • Graded, not propagated, gates vary.

Summation Effects

  • IPSPs make action potentials less likely by increasing negativity in resting membrane potential; critical for slowing contractions in heart/digestion.

  • Spatial Summation:

    • Multiple presynaptic structures firing simultaneously, leading to summed signals over space.

  • Temporal Summation:

    • One or few presynaptic structures firing in quick succession, leading to summed signals over time.

Action Potential Propagation

  • An action potential typically excites adjacent membrane portions.

  • Carried by inward-diffusing Na+ ions.

  • Positive charges increase voltage in adjacent membrane segments, raising them to threshold.

  • Additional Na+ gates open, allowing signal to travel down the membrane length.

  • Refractory Period

    • Follows each action potential; another cannot occur until the baseline is restored, yielding one-way signal propagation.

Neurotransmitter Release Mechanism

  • Occurs in the neurotransmission zone of neurons following the action potential reaching voltage-regulated Ca++ gates;

  • Ca++ rushes into the cell, triggering neurotransmitter vesicles to fuse with the membrane and release into the synapse.

  • Post-release, neurotransmitters must be cleared to prevent ongoing receptor stimulation.

Faulty Neurotransmitter Breakdown Implications

  1. Acetylcholine:

    • Decreases heart rate by initiating IPSPs in cardiac muscle.

    • Excess acetylcholine slows the heart, deficit increases it.

    • ACHE (acetylcholinesterase) breaks down acetylcholine, speeding up heart rate when in excess.

  2. Norepinephrine/Epinephrine:

    • Increases heart rate via sympathetic motor system stimulation.

    • Breakdown reduces heart rate; MAO (monoamine oxidase) reduces both norepinephrine and serotonin levels.

Factors Affecting Signal Transmission Speed

  1. Diameter of Neuron:

    • Larger diameter results in faster transmission.

  2. Myelination:

    • Schwann Cells (PNS) and Oligodendrocytes (CNS) wrap axons, forming myelin sheaths which insulate axons and increase signal speed.

    • Nodes of Ranvier increase speed of signals by allowing saltatory conduction, saving energy with reduced need for Na+/K+ pumps.

Somatic Nervous System

  • Function: Connects muscles to the central nervous system.

  • Neurotransmitter: Acetylcholine.

  • Receptor Type: Nicotinic type 2.

  • Motor End Plate: Tight fit between neuron and muscle fiber; neuron innervates multiple fibers.

  • Motor Unit: Somatic motor neuron and all muscle fibers it innervates; varies in size (small units for precise movements vs. large units for gross movements).

Normal Form Curve

  • Demonstrates three periods associated with single muscle twitch:

    • Latent Period (L): time between stimulus application and twitch onset.

    • Contraction Period (C): time of muscle contraction.

    • Relaxation Period (R): time of muscle relaxation.

    • Latent period: approx. 0.2 msec; total twitch including L period: approx. 100 msec.

Summation Mechanisms in Muscle Contraction

  • Spatial Summation (Motor Unit Recruitment):

    • Motor units are recruited based on stimulus strength. Sub-threshold stimuli do not create muscle twitches. Maximal stimulus recruits all motor units.

  • Temporal Summation:

    • Repeated maximal stimuli, with reduced relaxation time leads to sustained contractions (tetany).

Muscle Anatomy

  • Hierarchy of Organization (refer to muscle structure figures):

    • Muscle: Made of bundles called muscle fasciculi.

    • Muscle Fasciculi: Comprised of multinucleate muscle fibers.

    • Muscle Fibers: Contain smaller units called myofibrils.

    • Myofibrils: Comprised of myofilaments (proteins).

    • Sarcomere: Functional unit of skeletal muscle, containing organized myofilaments.

Structural Components of Myofilaments

  • Thick Filaments: Comprised of approx. 200 myosin molecules; myosin heads act as cross-bridges, binding with thin filaments.

  • Thin Filaments: Comprised of actin, tropomyosin, and troponin.

    • Actin: Main structural protein, has binding sites for myosin.

    • Tropomyosin: Covers cross-bridge binding sites; bound to troponin.

    • Troponin: Bound to tropomyosin; has Ca++ binding sites.

  • Titin: Maintains arrangement of filaments; attached to Z-line and thick filament.

  • Tropomyosin and troponin prevent actin-myosin interaction at rest.

Steps of Skeletal Muscle Contraction

  1. Action potential occurs in somatic motor neuron.

  2. Acetylcholine released into neuromuscular synapse.

  3. Acetylcholine binds nicotinic type 2 receptors on muscle membrane.

  4. End Plate Potential (EPP) occurs, sparking an action potential in the muscle.

  5. Action potential propagates along muscle membrane and into T-tubules.

  6. Voltage change opens voltage-regulated Ca++ gates.

  7. Ca++ rushes out from the sarcoplasmic reticulum.

  8. Ca++ binds to troponin, initiating a conformational change.

  9. Tropomyosin shifts to expose cross-bridge binding sites.

  10. Myosin bonds with actin, triggering contraction.

  11. Each muscle fiber shortens to approximately 65% of its original length during contraction.

ATP (Adenosine Triphosphate) in Contraction

  • 1 ATP is consumed per cross-bridge cycle.

  • Myosin head's power stroke does not require ATP; it is needed for detachment and recocking.

  • ATP is also needed for Ca++ pumps during relaxation.

Effects of Fatigue on Muscle

  1. Reduced contraction force due to decreased ATP.

  2. Extended relaxation due to insufficient ATP for Ca++ pumps.

  3. May lead to muscle cramps and lactic acid buildup (burning sensation).

  4. Rigor Mortis: Occurs post-death; depleted ATP causes prolonged muscle contraction due to cross-bridges remaining attached.

Autonomic Nervous System

  • Controls visceral functions such as heart rate, digestion, and breathing.

  • Comprises two branches: Sympathetic and Parasympathetic:

    • Typically antagonistic, most organs receive innervation from both branches, utilizing two-neuron pathways.

Neuro-neuronal Synapses in Autonomic System

  • Sympathetic Branch:

    • Ganglia located along the spinal cord.

    • Postsynaptic neurotransmitter: Norepinephrine (95%), Epinephrine (5%).

    • Receptors on muscle: α or β receptors (EPSP or IPSP depending on the organ).

  • Parasympathetic Branch:

    • Variable neuro-neuronal synapse locations.

    • Postsynaptic neurotransmitter: Acetylcholine (EPSP).

    • Muscle receptors: Muscarinic (M) receptors (EPSP or IPSP).

Synapses in the Autonomic System

  • Cholinergic Synapses:

    • Acetylcholine released at all neuro-neuronal synapses (sympathetic and parasympathetic).

  • Adrenergic Synapses:

    • Norepinephrine/Epinephrine released in sympathetic neuro-muscular synapses.

    • Created predominately from adrenal medulla release (80% epinephrine).

The Adrenal Gland

  • Sits above kidneys; functions as a ganglion without axons.

  • Adrenal Cortex: Major steroid-producing gland.

  • Adrenal Medulla: Releases a mixture of norepinephrine and epinephrine into the bloodstream, acting as a hormone during stress responses (adrenaline rush).

Nerve Locations in Autonomic System

  • Parasympathetic Nerves: Cranial or sacral nerves.

    • Vagus Nerve (Cranial X): Major parasympathetic supply to heart, bronchi, digestive organs.

  • Sympathetic Nerves: All thoracic and lumbar nerves.

  • Important to note: Sympathetic and parasympathetic nerves are separate to avoid contradictory signals.

Blood Flow Redistribution

  • Most blood vessels are sympathetic-innervated only.

  • Receptors:

    • α1 Receptors: Vasoconstriction (EPSP), increasing blood pressure.

    • β2 Receptors: Vasodilation (IPSP) in coronary vessels, increasing blood flow to heart and skeletal muscles.

  • Few parasympathetic-innervated blood vessels serve reproductive tissues, causing vasodilation during arousal.

Drugs Affecting the Nervous System

  • Atropine: Blocks M receptors, impeding parasympathetic responses.

  • Curare: Binds to nicotinic receptors, causing paralysis.

  • Pseudoephedrine: Stimulates α receptors, reducing mucus secretion.

  • Isoproterenol: Stimulates β receptors, expands bronchi, alleviating asthma-related constriction.