NURS 207 (N01) Nervous System Resting Membrane Potential & Neuron PDF

NURS 207 (N01) Nervous System Resting membrane potential and neuron Nov 18, 2024 Dr. P. Lee  Objectives: 1) Know the basic principle of how the resting membrane potential is generated 2) Describe the anatomy of a typical neuron an...

NURS 207 (N01) Nervous System Resting membrane potential and neuron Nov 18, 2024 Dr. P. Lee  Objectives: 1) Know the basic principle of how the resting membrane potential is generated 2) Describe the anatomy of a typical neuron and its corresponding physiological functions Review  Membrane permeability Phospholipid bilayer of living cell membranes are impermeable to charged molecules e.g. Na+ , K+ , Cl- , and Ca++ → They are also insoluble in the hydrophobic membrane core → The same for large water-soluble molecules such as protein, nucleic acids, sugars, etc. → Transportation of these molecules across the cell membrane require channels Small uncharged polar molecules can cross the membrane freely e.g.) CO2, O2, NH3,(ammonia) and water (mostly with aquaporins)  Electrolytes distribution Major electrolytes in interstitial fluid are: → Na+, Cl-, and HCO3- Major electrolytes in intercellular fluid are: → K +, HPO42- (phosphate ion), and negatively charged proteins  Dominant cations and anions distribution between the extra and intracellular compartments Extracellular fluid Intracellular fluid Cations (+ve ions) ❖ Na+ ❖ K+ Anions (-ve ions) ❖ Cl- ❖ Phosphate ions & -ve charged proteins It is the selective permeability of the plasma membrane which creates the uneven distribution of electrolytes that generates the electrochemical disequilibrium across the plasma membrane  Electrical properties of the cell membrane Plasma membranes can be described as an ionic conductance (ionic currents can pass through) It is the concentration gradient that dictate the direction of flow across the membrane And as a capacitor (ability to hold charges) It is the electrical gradient that generates the transmembrane potential (electrical voltage differences between the intra and extracellular space)  Generation of membrane potential Cell and solution are electrically and chemically at equilibrium The cell membrane acts as an insulator to prevent free movement of ions between the intracellular and extracellular compartments Since with 3 Na+- K+ ATPase creates +ve ions out ionic concentration and 2 +ve gradients ions in, net (3 Na+ out and 2 K+ in) intracellular ion is -1 With one extra +ve (one less ion located +ve) Intracellular fluid Extracellular fluid extracellularly, it become +ve 1 −2 −1 0 +1 +2 Absolute charge scale Intracellular fluid Extracellular fluid −2 −1 0 +1 +2 Relative charge scale → extracellular fluid set to 0 (ground) → With relative charge scale set at zero for the extracellular space, resting membrane potential become negative 2 for this cell  K+ leak channels Plasma membrane typically has more K+ leak channels than Na+ leak channels K+ will leak out to the extracellular space due to concentration gradients → -ve ions inside the cell will attempt to follow the efflux of K+ (+ve and –ve ions attract each other) → However, plasma membrane is impermeable to –ve ions (that creates a condition that more –ve ions remain trapped inside the cell → i.e.) Leakage of K+ through the K+ leak channels is partly responsible for the formation of resting membrane  Equilibrium potential Loss of +ve ions (K+) intracellularly (through Na+- K+ ATPase and K+ leakage channels) creates an electrical gradient (more -ve ions intracellularly) The –ve charged ions and molecules will try to pull K+ back to the intracellular space (+ve and –ve ions attract each other)) When these opposing forces (concentration gradient and Na+ Cl- electrical gradient) are equal, K+ Concentration gradient Na+ K+ Electrical the net movement of electrolytes K+ Pr- Pr- K+ gradient + 1 Cl- Pr- - are zero. The membrane − 1 Pr Cl- Na+ Cl- Na+ potential at this point is know as equilibrium potential (Eion) Resting membrane potential  Resting membrane potential All living cells have membrane potential → Chemical and electrical disequilibrium occurs between the intracellular and interstitial fluid at resting state (not being stimulated) → The electrical disequilibrium creates an electrical gradient between the intracellular and interstitial fluid ▪ This electrical gradient generates a transmembrane potential between the intracellular and interstitial fluid ▪ At resting state, transmembrane potential (also as resting membrane potential) is a measure of the electric charges inside relative to outside of the cell ▪ There are more -ve than +ve charges intracellularly ▪ Resting membrane potential is normally –ve in value  Stimulation of plasma membrane Stimulus Intracellular fluid Extracellular fluid Na+ influx + K + Na+ Na + Na + K+ + K + Na+ K Known as Na + Na+ Na+ K + depolarization K + K Na+ Na+ Na+ K+ + (intracellular + K become more +ve) K K + + K + Na+ Na+ + Na + K efflux Na Na+ Na+ Na+ K + K + K + Follows by Na+ Na+ Na+ repolarization Na + K + K + (intracellular ionic K +K + Cl - charges back to the baseline level) 3 Na+ Na+- K+ ATPase restores 2 K+ HPO42- the electrolytes distribution Na+- K+ ATPase beck to resting condition  Resting state of plasma membrane Some K+ and Na+ leak channels are found within the plasma membrane (more so for K+ leak channels) → Requires Na+- K+ ATPase transporters (electrogenic pump) to maintain ionic concentration gradients across the membrane during the resting state  At resting state Major electrolytes Major electrolytes in interstitial fluid in intracellular fluid Na+ 145 mM Na+ 15 mM Osmolarity: 290 mOsm/L Cl- 116 mM Cl- 20 mM K + 4.5 mM K + 120 mM 3 Na+ Protein 0 mM Protein 4 mM Osmolarity: 290 mOsm/L Na+- K+ ATPase 2 K+ → The extra and intracellular compartments are in a dynamic steady state, but are not at equilibrium → They are in osmotic equilibrium (no movement of H2O) but with chemical and electrical disequilibrium → Intracellular space contains more –ve ions  Equilibrium potential of a living cell Equilibrium potential for a single ion type (Eion) can be calculated by using Nernst equation Nernst equation: Eion = (61/z) log ([ion]extra / [ion]intra) Where: Eion equilibrium potential in mV z valence (charge) [ion]extra ion concentration outside the cell [ion]intra ion concentration inside the cell 61 constant = 2.303 RT/F @ 37oC R gas constant T temperature in Kelvin F Faraday constant  Ion distribution for K+ and the equilibrium potential calculated from the Nernst equation Extracellular Intracellular Equilibrium concentration concentration potential Ion (mM) (mM) (mV) K+ 4.5 120 -85.6 Implies: ✓ Higher intracellular K+ concentration causes a net efflux of K+ into extracellular space ✓ Tendency of K+ efflux due to the concentration gradient can be counter balanced exactly by a negative equilibrium potential of -85.6 mV  Resting membrane potential At rest, the cell is in a dynamic steady state, but are NOT at equilibrium i.e. A condition of dynamic steady state with chemical and electrical disequilibrium is established Metabolic energy MUST be used to maintain the ionic gradients across the membrane  +40 +20 Membrane potential difference (Vm) Membrane potential (mV) 0 −20 Vm decreases Vm −40 increases −60 −80 −100 Depolarization Repolarization Hyperpolarization −120 Time (msec) Figure 5.26 Depolarization → Membrane potential becomes less -ve than the resting membrane potential Repolarization → Membrane potential return back to the resting membrane potential Hyperpolarization → Membrane potential becomes more –ve than the resting membrane potential  Important concepts Nernst equation: Eion = (61/z) log ([ion]extra / [ion]intra) Equilibrium potential (@ rest) is determined primarily by: → Concentration gradient of ion (static condition at resting state) Electrical signals in an excitable cell, permeability to K+, Na+, and Cl– also need to be considered (dynamic) Goldman-Hodgkin-Katz (GHK) equation: { (Pk[K+]extra + PNa[Na+]extra + PCl[Cl-]intra } Vm = 61 x log { (Pk[K+]intra + PNa[Na+]intra + PCl[Cl-]extra }  Describe the anatomy of a typical NEURON and its corresponding physiological functions  Nervous system - Introduction ❖ Neuron is the functional unit of the nervous system For the transmission and integration of information → Signal is in the form of electrical (graded and action potential) and chemical (neural transmitter) → Between the nervous system and the rest of the body systems, which involves: ✓ Receiving: various form of stimuli traveling from peripheral to central through sensory neurons ✓ Integrating: within the central nervous system (CNS) ✓ Responding: triggers body function through efferent neuron from CNS to peripheral nervous system (PNS)  Neuron Neuron is also known as nerve cell (nerve is a cable like structure containing bundle of neurons ) → An excitable cell ✓ Capable of changing its membrane potential by either opening or closing the ion channels ✓ Can process and transmit information through chemical or electrical signals → Containing processes (branches) for either receiving or sending information → With a wide diversity of shape Cell body Structural classification of neurons Not next to the cell body Cell body Cell body → With multiple → With two processes → With only one processes (branches) projected from the process projected projected from the cell body from the cell body cell body Sensory Neurons Interneurons of CNS Efferent Neurons Somatic senses Neurons for Dendrites smell and vision Dendrites Axon Dendrites Schwann cell Axon Axon Axon Axon terminal Structural Categories Pseudounipolar Bipolar Anaxonic Multipolar Pseudounipolar Bipolar neurons Multipolar CNS A typical multipolar efferent neurons have a have two Anaxonic CNS interneurons are highly neuron has five to seven single process relatively equal interneurons branched but lack long dendrites, each branching called the axon. fibers extending have no apparent extensions. four to six times. A single During development, off the central axon. long axon may branch the dendrite fused cell body. several times and end at with the axon. enlarged axon terminals. Structural configuration is functional related  Functional classification of neurons Sending electrical impulses to CNS Receiving electrical impulses from CNS  Functional classification of neurons 1) Sensory neurons Usually are unipolar in structure → Bipolar is associated with special sensory located within olfactory, retina, and inner ear With sensory receptors at the dendrites or with their dendrites located just next to the cells that act as sensory receptors → Once activated, it conveys the information in the form of electrical signal (action potential) to the CNS through cranial or spinal nerves Also known as afferent neurons (towards CNS)  Functional classification of neurons 2) Interneurons Can be anaxonic (absent of axon) or multipolar in structure Mainly within CNS → between sensory and motor neurons → Integrate sensory information from sensory neurons → Then send the information to the appropriate motor neurons to elicit a response Also known as association neurons  Functional classification of neurons 3) Motor neurons Are multipolar in structure → Convey information in the form of action potentials from CNS towards effector (effector can be motor unit for muscle contraction or glands for secretion) Also known as efferent neurons A typical neuron  Neuron A typical neuron has 3 regions: cell body, dendrites, and axon Parts of a Neuron Nucleus Axon Axon (initial Myelin sheath Postsynaptic hillock segment) neuron Synapse: The region where an Presynaptic Synaptic Postsynaptic axon terminal axon terminal cleft dendrite communicates Cell with its Dendrites body postsynaptic target cell Input Integration Output signal signal Dendrites Cell body Axon 1) Cell body (soma) With nucleus and all the organelles found within a typical excitable cell General occupies only 1/10 or less of the total neuron volume Proteins produced by the nucleus do not migrate far from the nucleus through diffusion i.e. Need transporting system for these proteins Containing cytoskeleton (microtubule) spreading outward into the other structures (dendrites and axon) of the neuron → Microtubule is essential for intracellular transport to and form structures 2) Dendrites Parts of a Neuron Nucleus Axon Axon (initial Myelin sheath Postsynaptic hillock segment) neuron Synapse: The Presynaptic Synaptic Postsynaptic region where an Dendrites Cell body axon terminal cleft dendrite axon terminal communicates with its postsynaptic Input Integration Output signal target cell signal Are thin branches (processes) of a neuron that receive incoming information from neighboring cell i.e. Allowing one neuron to communicate with multiple neurons Signals from one neuron are usually transmitted down the axon (direction of flow is referred to as anterograde neurotransmission → forward motion) 2) Dendrites Parts of a Neuron Nucleus Axon Axon (initial Myelin sheath Postsynaptic hillock segment) neuron Synapse: The Presynaptic Synaptic Postsynaptic region where an axon terminal dendrite axon terminal Cell cleft Dendrites communicates body with its postsynaptic target cell Input Integration Output signal signal Electrical signals in the form of graded potentials from dendrites are integrated within the cell body → Then through the axon (electrical) → Reaching the presynaptic axon terminal (electrical) → Through the synaptic cleft (electrical is converted into chemical in the form of neurotransmitter) → Into the postsynaptic dendrite (chemical converted into electrical)  Presynaptic 2) Dendrites axon terminal Synaptic cleft Parts of a Neuron Nucleus Axon Axon (initial Myelin sheath Postsynaptic hillock segment) neuron Synapse: The region where an Presynaptic Synaptic Postsynaptic axon terminal axon terminal cleft dendrite communicates Cell Dendrites with its body postsynaptic target cell Input Integration Output signal signal Postsynaptic dendrite Synaptic communication → Neural information in the form of neurotransmitter → Neurotransmitter is released at the presynaptic axon terminal and move through synaptic cleft → Neurotransmitter enters the neighboring neurons through postsynaptic dendrites 2) Dendrites Dendrites also contain dendritic spines, the specialized protrusions from the dendritic shaft Excitatory synapses (red) Spine head Spine neck Inhibitory synapses (blue) Spines 2) Dendrites Excitatory synapses (red) Spine head Spine neck Inhibitory synapses (blue) Spines Figure 8.24 The presence of dendritic spines enable an increase in the number of possible contact sites between neuron and its neighboring cells Many dendritic spines contain polyribosomes and are capable to synthesize their own proteins 2) Dendrites Excitatory synapses (red) Spine head Spine neck Inhibitory synapses (blue) Spines Because of the ability for the dendritic spines to produce proteins, these proteins can be transmitted from the dendritic spines, through the synaptic cleft, and back to the presynaptic axon terminal (refer to as retrograde transport i.e. backward) 2) Dendrites Parts of a Neuron Nucleus Axon Axon (initial Myelin sheath Postsynaptic hillock segment) neuron Synapse: The region where an Presynaptic Synaptic Postsynaptic axon terminal axon terminal cleft dendrite communicates Cell Dendrites with its body postsynaptic target cell Input Integration Output signal signal These retrograde messengers, released from the postsynaptic dendritic spines, enter the presynaptic axon terminals to exert their effects with respect to the regulation or feedback of the chemical neurotransmission release in the presynaptic axon terminals 2) Dendrites Excitatory synapses (red) Spine head Spine neck Inhibitory synapses (blue) Spines The morphology of the dendritic spines are very dynamic (shape & size are constantly changing) The morphological changes of the dendritic spines are believed to be associated with learning and memory 3) Axon Each neuron has a single axon Axon is originated from a specialized region of the soma call axon hillock (trigger zone) Parts of a Neuron Nucleus Axon Axon (initial Myelin sheath Postsynaptic hillock segment) neuron Synapse: The region where an Presynaptic Synaptic Postsynaptic axon terminal axon terminal cleft dendrite communicates Cell Dendrites with its Axon body postsynaptic target cell Input Integration Output signal signal → Axon hillock (trigger zone) is the area determining whether the electrical signals from the dendrites can proceed forward through the axon 3) Axons Axon then branches along its shaft to form swelling axon terminals (as the presynaptic axon terminals) at each collateral end Presynaptic axon terminal contains mitochondria and membrane-bound vesicles filled with neurocrine molecules such as neurotransmitters, neuromodulator, or neurohormone 3) Axons The main function of axon is to transmit electrical signals from the soma of a neuron to its presynaptic axon terminals where information is transformed from electrical to chemical and passes onto the neighboring cells Axons are also capable of transporting vesicles and mitochondria, produced by the nucleus within the soma, to the axon terminal and return the synaptic vesicle from the axon terminal back to soma for recycling (process known as axonal transport) FAST AXONAL TRANSPORT Peptides are synthesized on rough ER and packaged by the Golgi apparatus. Rough Fast axonal transport walks endoplasmic vesicles and mitochondria reticulum Golgi along microtubule network. apparatus Soma Vesicle contents are released by exocytosis. Synaptic vesicle Retrograde fast Lysosome axonal transport Synaptic vesicle recycling Old membrane components digested in lysosomes Microtubule A typical neuron  Axonal transport Transport of protein filled vesicles, produced by the nucleus of a neuron, is facilitated by the microtubular-associated motor proteins Motor proteins usually composed of: - 2 heads (bind to the microtubules) - a neck - a tail region that is capable to bind with organelles such as vesicle that needs to be transported across the cytosolic space Tail Organelle Motor protein Neck Head ATP Direction of movement Cytoskeletal fiber  Axonal transport Heads can alternately bind to the microtubules, then release and step forward → Also refer to as walking along the cytoskeleton fibers (requires ATP as the energy source) Organelle → Can be in either directions Motor protein ATP Direction of movement Cytoskeletal fiber ▪ Shingles (a painful skin rash and blasters condition) is cause by the migration of the varicella zoster virus from the soma of a neuron (resided there during their latent period) to the skin using this axonal anterograde transport mechanism  Important concepts Neurons Information goes from receiving site (dendrites or cell body) to the axon hillock in the form of graded potentials Electrical signals in the form of action potentials are initiated within the region of axon hillock or trigger zone and propagated unidirectionally to the presynaptic terminal Axons are specialized to carry electrical signals unidirectionally and chemical signals bi-directionally There is no cytoplasmic continuity between neurons (each neuron is an isolated unit) Neurons do not connect indiscriminately  Sample questions 1) Which of the following statement is correct in describing sensory neuron? a) it is usually anaxonic in structure b) it conveys information to the CNS c) it sends information to the motor unit d) it is part of the interneuron 2) Axon transmits: a) electrical information only b) chemical information only c) both electrical and chemical information d) none of the above is correct  Sample questions 3) Which part of a neuron is normally receiving information from the neighboring cells? a) axon b) cell body c) dendrites d) axon hillock 4) Which part of a neuron is also known as the trigger zone? a) axon b) cell body c) dendrites d) axon hillock  Sample questions 5) Neurotransmitter is released to the extracellular space from: a) presynaptic axon terminal b) postsynaptic axon terminal c) dendrites d) cell body 6) A depolarizing graded potential: a) makes the membrane more polarized b) makes the membrane less polarized c) occurs when chloride enters the cytosol d) occurs when anion enters the cytosol  Sample questions 7) Depolarization occurs when: a) membrane potential is at its resting membrane potential b) membrane potential is more –ve than the resting membrane potential c) membrane potential is less –ve than the resting membrane potential d) membrane potential is equal to zero 8) Hyperpolarization occurs when: a) membrane potential is at its resting membrane potential b) membrane potential is more –ve than the resting membrane potential c) membrane potential is less –ve than the resting membrane potential d) membrane potential is equal to zero  Answer to sample questions 1) b 2) c 3) c 4) d 5) a 6) B 7) C 8) B