Neuro Physiology

• Generation and Propagation

  - places substantial demands on neurons energy resources

  - mitochondria generates energy needed by active neuron
• Functional classifications of neurons

  1. Sensory neurons
  2. Motor neurons
  3. Interneurons
• Sensory Neurons

  - Unipolar

  - Cell bodies grouped in sensory ganglia

  - Processes (afferent fibers) extend from sensory receptors to CNS

  - Somatic sensory neurons

  • Monitor external environment

  - Visceral sensory neurons

  • Monitor internal environment
• Types of Sensory Receptors

  - Interoceptors

  • Monitor internal systems (e.g., digestive, urinary)

  • Internal senses (stretch, deep pressure, pain)

  - Exteroceptors

  • Monitor external environment (e.g., temperature) 

  • Complex senses (e.g., sight, smell, hearing)

  - Proprioceptors

  • Monitor position and movement of skeletal muscles and joints
• Motor neurons

  - Carry instructions from CNS to peripheral effectors

  • Via efferent fibers (axons) 

  - Somatic motor neurons of SNS 

  • Innervate skeletal muscles

  - Visceral motor neurons of ANS

  • Innervate all other peripheral effectors

  • Smooth and cardiac muscle, glands, adipose tissue

  - Signals from CNS to visceral effectors cross autonomic ganglia that divide axons into

  • Preganglionic fibers***

  • Postganglionic fibers***
• Interneurons

  - Most are in brain and spinal cord 

  • Some in autonomic ganglia

  - Located between sensory and motor neurons

  - Responsible for

  • Distribution of sensory information

  • Coordination of motor activity 

  - Involved in higher functions

  • Memory, planning, learning
• Neuroglia

  - Support and protect neurons 

  - Make up half the volume of the nervous system

  - Many types in CNS and PNS

  • Astrocytes

  • Ependymal cells 

  • Oligodendrocytes

  • Microglia
• Astrocytes

  - Have large cell bodies with many processes 

  - Function to

  • Maintain blood brain barrier (BBB)

  • Create three-dimensional framework for CNS

  • Repair damaged nervous tissue

  • Guide neuron development

  • Control interstitial environment
• Ependymal cells

  - Form epithelium that lines central canal of spinal cord and ventricles of brain

  - Produce and monitor cerebrospinal fluid (CSF)

  - Have cilia that help circulate CSF
• Oligodendrocytes

  - Have small cell bodies with few processes

  - Many cooperate to form a myelin sheath

  • Myelin insulates myelinated axons

  • Increases speed of action potentials 

  • Makes nerves appear white

  - Internodes — myelinated segments of axon

  - Nodes (nodes of Ranvier) lie between internodes

  • Where axons may branch

  - White matter

  • Regions of CNS with many myelinated axons

  - Gray matter of CNS

  • Contains unmyelinated axons, neuron cell bodies, and dendrites
• Microglia

  - Smallest and least numerous neuroglia

  - Have many fine-branched processes

  - Migrate through nervous tissue

  - Clean up cellular debris, wastes, and pathogens
• Neuroglia in PNS

  - Insulate neuronal cell bodies and most axons 

  - Two types

  • Satellite cells

  • Schwann cells
• Satellite cells

  - Surround ganglia (clusters of neuronal cell bodies) 

  - Regulate interstitial fluid around neurons
• Schwann cells (neurolemmocytes)

  - Form myelin sheath or indented folds of plasma membrane around axons

  - Neurolemma — outer surface of Schwann cell

  - A myelinating Schwann cell sheaths only one axon

  • Many Schwann cells sheath entire axon
• Membrane potential

  - Living cells have membrane potential that varies from moment to moment & depends on activities

  - Resting membrane potential

  • The membrane potential of a resting cell

  • Difference between + and – ions on either side of the membrane

    • Inside of cell is negative relative to outside of cell (ICF is -70mV)
• Membrane Potential

  - Graded potential

  • Temporary, localized change in resting potential, decreases with distance

  • Caused by a stimulus

  • if big enough can trigger action potential

  - Action potential

  • Is an electrical impulse

  • Produced by graded potential

  • Propagates along surface of axon to synapse
• Membrane Potential

  - Equilibrium potential

  • Membrane potential at which there is no net movement of a particular ion across cell membrane

  • K+ =–90mV

  • Na+ =+66mV

  • Plasma membrane is highly permeable to K+

  - Explains similarity of equilibrium potential for K+ and resting membrane potential (–70 mV)

  • Resting membrane’s permeability to Na+ is very low

  - Na+ has a small effect on resting potential
• Resting membrane potential

  - Three important concepts

  1. The extracellular fluid (ECF) and intracellular fluid (cytosol) differ greatly inionic composition 

  • Extracellular fluid: high concentrations of Na+ and Cl–

  • Cytosol contains high concentrations of K+ and negatively charged proteins (stimulates change in membrane potential)

  2. Cells have selectively permeable membranes

  3. Membrane permeability varies by ion (maintains homeostasis)
• Resting Membrane Potential

  - Na+ and K+ are the primary determinants of membrane potential 

  • Na+ and K+ channels are either passive or active

  - Passive ion channels (leak channels)

  • Are always open

  • Permeability changes with conditions

  - Active ion channels (gated ion channels)

  • Open and close in response to stimuli

  • At resting membrane potential, most are closed
• Processes that produce resting membrane

  - passive chemical gradient:

  • intracellular K+ is high, K+ leak channels move them out of cell

  • extracellular Na+ is high, Na+ leak channels move them into cell

  - Active Na+/K+ Pumps

  - passive electrical gradient:

  • K+ leaves more rapidly, more permeable, more positive charge outside

  • negatively charged protein molecules cannot cross, more negative inside

  - resting membrane potential: -70mV
• Passive processes

  - Passive processes acting across cell membrane, influences how specific ions will move across membrane

  • Chemical gradients

  - Concentration gradients of ions (Na+, K+) 

  • Electrical gradients

  - Charges are separated by cell membrane

  - Cytosol is negative relative to extracellular fluid

  • Electrochemical gradient

  - Sum of chemical and electrical forces acting on an ion across the membrane

  - A form of potential energy
• Electrochemical Gradients at resting potential:

  - intracellular K+ is higher, chemical gradient drives K+ out, but K+ is attracted to negative environment inside cell and repelled by positive charges outside cell

  • net electrochemical gradient pushes K+ out (small)

  • if freely permeable, pressure in and out are equal
• Electrochemical gradient at resting potential:

  - intracellular Na+ is lower, chemical gradient tends to drive Na+ in, Na+ is also attracted to negative environment inside cell and repelled by positive outside cell

  • net electrochemical gradient pushes Na+ in (big)

  • if freely permeable, would move differently
• Active process:

  - Active processes across the membrane 

  • Sodium–potassium exchange pump

  - Powered by ATP

  - Ejects 3 Na+ for every 2 K+ brought in

  - Balances passive forces of diffusion

  - Stabilizes resting membrane potential (–70 mV)

  • When ratio of Na+ entry to K+ loss, passive channels is 3:2

  - at resting potential, Na+ is ejected as quickly as they enter the cell to maintain homeostasis and resting membrane potential
• Active process - Active channel

  - Types of active channels, exists to respond to specific stimuli

  1. Chemically gated ion channels
  2. Voltage-gated ion channels
  3. Mechanically gated ion channels
• Chemically Gated Ion Channels

  - Open when they bind specific chemicals (e.g., ACh)

  - Found on cell body and dendrites of neurons

  - binding sites allow opening of gate to let product in
• Voltage gated ion channels

  - Respond to changes in membrane potential, extracellular changes

  - Found in axons of neurons and sarcolemma of skeletal and cardiac muscle cells

  - Activation gate opens when stimulated

  - Inactivation gate closes to stop ion movement when stabilized

  - Three possible states

  1. Closed but capable of opening
  2. Open (activated)
  3. Closed and incapable of opening (inactivated)
• Mechanically Gated ion channels

  - Respond to membrane distortion

  - Found in sensory receptors that respond to touch, pressure, or vibration
• Graded vs Action Potential

  - Graded potential

  • Temporary, localized change in resting potential

  • Caused by a stimulus that often trigger cell functions

  • Exocytosis of glandular secretions

  - Action potential

  • Brief, rapid, large (100mv) change in membrane potential

  • Needed for neurons to conduct impulse, responses in bodies

  • Produced by graded potential
• Graded potential

  - Graded potentials (local potentials)

  • Changes in membrane potential

  - cannot spread far from site of stimulation

  • Produced by any stimulus that opens gated channels u 

  - E.g. a resting membrane is exposed to a chemical

  • Chemically gated Na+ channels open

  • Sodium ions enter cell

  • Membrane potential rises (depolarization)

  • Sodium ions move parallel to plasma membrane

  - Producing local current

  - Which depolarizes nearby regions of plasma membrane (graded potential)

  - Change in potential is proportional to stimulus
• Characteristics of graded potentials

  - Membrane potential is most changed at site of stimulation; effect decreases with distance

  - Effect spreads passively, due to local currents

  - Graded change in membrane potential may involve depolarization or hyperpolarization

  - Stronger stimuli produce greater changes in membrane potential and affect a larger area

  - Often trigger specific cell functions

  • Example: exocytosis of glandular secretions

  - ACh causes graded potential at motor end plate at neuromuscular junction
• Graded potential sequence

  - At resting membrane, closed chemically gated sodium ion channels

  1. Stimulation: membrane exposed to chemical that opens the Na+ ion channels, allow Na+ influx

  2. Graded potential: spread of Na+ along inner surface produces a local current that depolarizes adjacent portions of the plasma membrane
• Graded Potential

  - Repolarization

  • When the stimulus is removed, membrane potential returns to normal

  - Hyperpolarization

  • Results from opening potassium ion channels 

  • Positive ions move out, not into cell

  - Opposite effect of opening sodium ion channels 

  • Increases the negativity of the resting potential
• Graded Sequence

  - chemical stimulus applied, depolarization (more positive), chemical stimulus removed, repolarization (more negative), resting membrane potential

  - chemical stimulus applied, hyperpolarization, chemical stimulus removed, return to resting membrane potential

  
• Action potential (nerve impulses)

  - Propagated changes in membrane potential

  - Affect an entire excitable membrane

  - Begin at initial segment of axon

  - Do not diminish as they move away from source

  - Stimulated by a graded potential that depolarizes the axolemma to threshold

  • Threshold for an axon is –60 to –55 mV, once reached, action potential is initiated
• Action potential

  - All-or-none principle

  • Any stimulus that changes the membrane potential to threshold

  - Will cause an action potential 

  • All action potentials are the same

  - No matter how large the stimulus

  • An action potential is either triggered or not triggered
• Generation of action potentials

  - Step 1: Depolarization to threshold

  - Step 2: Activation of voltage-gated Na+ channels

  • Na+ rushes into cytosol

  • Inner membrane surface changes from - to +

  • Results in rapid depolarization

  - Step 3: Inactivation of Na+ channels and activation of K+ channels

  • At +30 mV, inactivation gates of voltage-gated Na+ channels close

  • Voltage-gated K+ channels open

  • Repolarization begins

  • K+ moves out of cytosol
• Generation of action potential

  - Step 4: Return to resting membrane potential 

  • Voltage-gated K+ channels begin to close

  - As membrane reaches normal resting potential

  - K+ continues to leave cell

  - Membrane is briefly hyperpolarized to –90 mV

  • After all voltage-gated K+ channels finish closing

  - Resting membrane potential is restored

  - Action potential is over
• Refractory period

  - From beginning of action potential

  - To return to resting state

  - During which the membrane will not respond normally to additional stimuli
• Refractory period

  - Absolute refractory period (depolarization)

  • All voltage-gated Na+ channels are already open or inactivated

  • Membrane cannot respond to further stimulation

  - Relative refractory period

  • Begins when Na+ channels regain resting condition

  • Continues until membrane potential stabilizes

  • Only a strong stimulus can initiate another action potential

  (repolarization starts in absolute, ends in relative)