Nerve Cell Structure and Function - EASY

Nerve Cell Structure and Function

• Neurons are the nervous system's basic cellular units
• The human brain has approximately 10^11 neurons, each forming about 1,000 synapses
• There are roughly 10^14 synaptic connections in the human brain, creating a neural network for interconnected nerve cell communication

Nerve Cell Morphology

• Neurons contain specialized structures for organized information processing
• All neurons share basic features, despite variations based on function

Dendrites

• Short, branched cytoplasmic extensions
• Receive afferent signals from the environment
• Located near the cell body (soma)

Cell Body (Soma)

• Contains the nucleus and molecular machinery for gene expression, protein production, and cell metabolism

Axon

• A long cytoplasmic extension
• Transmits signals from the soma to end organs or other neurons
• Proteins are transported along microtubule "highways" by transport proteins

Kinesins

• Involved in anterograde transport (away from the soma)

Dyneins

• Involved in retrograde transport (towards the soma)

Myelin

• A phospholipid-rich sheath that surrounds axons
• Provides insulation for neurons and facilitates nerve transmission over long distances
• Composed of the plasma membrane of glial support cells

Oligodendrocytes

• Support cells in the CNS that support multiple neurons

Schwann Cells

• Support cells in the PNS that support one neuron

• The phospholipid fat in myelin gives axons a white appearance

• White matter consists of myelinated axons

• Grey matter consists of unmyelinated cell bodies

Terminal Boutons

• Specialized endings of the axon
• Enable communication to target tissues or other neurons via a synapse
• Synaptic Cleft: maintains association of presynaptic and postsynaptic elements, extensive cytoskeletal elements allow maintenance of structure and enzymatic degradation of excess neurotransmitter occurs here

Support Cells (Neuroglia) of the Neuron

Astrocytes

• Stain positive for glial fibrillary acidic protein (GFAP)
• Repair neurons, provide nutritional support, maintain the blood-brain barrier, and regulate CSF composition

Ependymal Cells

• A single cell layer that lines the ventricles
• Produce CSF in the choroid plexus and circulate CSF

Microglia

• Have irregular nuclei and little cytoplasm
• Become phagocytic in response to tissue damage

Oligodendroglia (Oligodendrocytes)

• Found in the CNS
• Myelinate up to 30 neurons each

Schwann Cells

• Found in the PNS; gaps between cells are called nodes of Ranvier
• Myelinate only one axon each; secrete growth factors and create a pathway for axonal regeneration

Neuron Classifications

• Based on the number of dendrites and axons

Unipolar

• One dendrite or one axon (sensory neurons)

Pseudo-unipolar

• One process that branches into a dendrite and an axon

Bipolar

• One dendrite and one axon

Multipolar

• Multiple dendrites and axons

Synapses

• Composed of the presynaptic axon terminal, synaptic cleft, and postsynaptic dendrite
• Two fundamental types exist

Chemical Synapses

• Convert an electrical signal into a chemical signal via a chemical receptor
• Highly regulated

Electrical Synapses

• Allow ions to flow directly between neurons without signal loss

Nerve Cell Membrane

• Consists of a lipid bilayer with embedded proteins
• Maintains the integrity of the intracellular environment, allows reception of signals, and regulates changes in the electrochemical state of the nerve cell

Membrane Proteins

• Two key classes are essential to nerve cell function: ion channels and neurotransmitter receptors

Ion Channels

• Regulate the passage of ions (Na+, K+, Cl−, Ca2+) into or out of the cell

Ungated Channels

• Constitutively open to their specific ion

Gated Channels

• Exist in three possible states: closed, open, or locked

Voltage-Gated Ion Channels

• More likely to open when there is a change in the electrical potential of the nerve cell membrane

Ligand-Gated Ion Channels

• More likely to open when a specific neurotransmitter binds to it

Neurotransmitter Receptors

• Present on the dendrites and plasma membrane of nonneuronal target cells
• Bind their respective neurotransmitter ligands released into the synaptic cleft

Nerve Cell Ions, Resting Membrane Potential, and Electrochemical Gradients

• The plasma membrane is semipermeable
• This allows some substances to pass between the intracellular and extracellular spaces while restricting others

Chemical Gradients

• Occur when the concentration of a solute differs on either side of the membrane
• Solute moves from high to low concentration until equilibrium is achieved

Electrical Gradients

• Occur when the solute possesses an electrical charge
• Na+, K+, Ca2+, Cl−, and HCO3− are electrically charged solutes with tightly controlled intracellular and extracellular concentrations
• Transmembrane movements are the basis of electrochemical signaling in neurons and muscle cells

Resting Membrane Potential (Em)

• Baseline electrical polarization of the cell membrane
• Defined as the difference in electrical potential between the inside and the outside of the cell: Em = Ein – Eout
• A typical human neuron has an Em of –60 to –70 mV

Factors Contributing to Negative Intracellular Space

• Negatively charged intracellular solutes that cannot cross the membrane
• The Na+,K+-ATPase enzyme transports 3 Na+ out and 2 K+ into the cell, resulting in a net loss of one positive charge
• Leakage of K+ out of the cell down its chemical gradient

Electrochemical Potential (μ)

• The sum of chemical and electrical potentials of ion X
• Defined by the equation: μ = μ0 + RTln[X] + zFE

Electrochemical Potential Difference (Δμ)

• Defined as Δμ = μin – μout
• Quantifies the electrochemical gradient, the combined chemical and electrical forces acting on an ion X
• Depends on the ratio of intracellular and extracellular ion concentrations, the ion's charge, and the Em of the cell

Nernst Equation

• Describes the equilibrium potential resulting from an ion being in equilibrium: Em = (–61.54 mV/z)log10([X]in/[X]out)
• Depends on the ion’s charge and its distribution across the cell membrane

Goldman Equation

• Em = (−61.54 mV)log[(PK* [K+]in /PK* [K+]out ) + (PNa+* [Na+]in /PNa+* [Na+]out ) +(PCl−* [Cl−]out /PCl−* [Cl−]in ) +...].
• Describes the steady state potentials for every ion gradient in the cellular and extracelular space
• The contribution of each ion is determined by the magnitude of the electrochemical gradient and the permeability or conductance of the membrane to that ion

Nerve Cell Function

• Neurons receive and transmit information in the form of electrochemical impulses
• This is a binary process: neurons are either "on" or "off"

Activation Thresholds

• To turn "on", a neuron requires a stimulus, one or more receptors for that stimulus, an intact plasma membrane, ion channels and ion gradients
• An activating stimulus will depolarize the membrane, or make it less negative with respect to extracellular space
• An inhibitory stimulus will hyperpolarize the membrane, or make it more negative

Threshold Membrane Potential

• Usually around -55 to -50 mV, must be attained for a stimulus to be sufficient for neuronal response

Conduction Velocity

• The change in Em decreases exponentially due to the resistance of the cytoplasm, depending on the distance from the stimulation site and the time from the initial stimulus

Factors Affecting Conduction Velocity

• Membrane resistance (rm)
• Cytoplasm resistance (ri)
• Membrane capacitance (cm)

Action Potential (AP)

• A self-propagating membrane depolarization cascade triggered when a stimulus depolarizes the membrane to the threshold value
• Considered the "on" state of the nerve cell
• An "all or nothing" response

Voltage-Gated Ion Channels

• The basis of the AP as they shift sequentially among three states: closed, open, and locked

Myelin, Nodes of Ranvier, and Saltatory Conduction

• APs are continually reinforced as they propagate down the axon via electrotonic conduction, or local current flows
• Myelin sheath ensures rapid AP propagation and prevents the loss of the conducting signal
• Nodes of Ranvier are gaps in the myelin sheath every 1 to 2 mm where AP regeneration occurs Saltatory Conduction: AP appears to start, move rapidly down the axon, slow down at a node of Ranvier to regenerate, and then continue down the axon quickly until it reaches the next node

Transmission Across the Synapse

• AP must be transformed from a membrane voltage into a transmissible, chemical signal to cross the synaptic cleft

Neurotransmitters

• The language that allows the AP to cross the synaptic cleft
• At rest, these chemical substances are stored in membrane-bound vesicles clustered at the axon terminals

Voltage-Gated Ca2+ Channels

• Open when an AP depolarizes the terminal membrane
• Ca2+ influx causes neurotransmitter vesicles to fuse with the cell membrane and release neurotransmitters into the synaptic cleft

Different Types of Neurotransmitters in the Central Nervous System and Their Functions

Acetylcholine

• In the PNS and CNS; muscarinic and nicotinic receptors
• Decreased levels: Alzheimer dementia

Dopamine

• Synthesized from tyrosine; precursor to norepinephrine
• Increased levels: psychosis, mania, and schizophrenia; decreased levels: Parkinson’s disease

γ-Aminobutyric Acid (GABA)

• Main inhibitory NT in the CNS
• Decreased levels: anxiety, epilepsy

Glutamate

• Main excitatory NT in the CNS
• Increased levels: epilepsy, schizophrenia, Alzheimer’s disease

Glycine

• Inhibitory NT; controls glutamate activity in the brain
• Indirect clinical effects through modulation of glutamate

Histamine

• Role in sleep modulation and satiety
• Decreased levels: sedation, increased appetite (weight gain)

Norepinephrine (NE)

• Precursor to epinephrine
• Increased levels: major depressive disorder; decreased levels: anxiety

Serotonin

• Monamine NT; synthesized from tryptophan; regulates body temperature, sleep, mood, sexuality
• Increased levels: schizophrenia; decreased levels: major depressive disorder, bipolar disorder, anxiety disorder

Pathophysiology of Neurons, Glia, and Electrical Conduction

• When neural tissue operates properly, it integrates and transmits signals rapidly to and from the brain; when neural tissue does not function normally (demyelination, tumor, etc), signal transmission may be compromised

Demyelinating Diseases

• Pathophysiology revolves around impaired signal conduction

Effects of Loss of Myelin

• Leads to increased time constant (τ), decreased length constant (λ), decreased conduction velocity, and decreased propagation distance
• Impaired conduction may affect afferent (sensory) and efferent (motor) functions, as well as more complex processes, such as cognition
• Symptoms depend on the type of nerve involved

Classification of Demyelinating Diseases

• Myelinoclastic: normal myelin is destroyed by toxic, chemical, or autoimmune substances
• Leukodystrophic: abnormal myelin degenerates

Channelopathies

• Rare disorders caused by genetic mutations in ion channel subunits or regulatory proteins, often with significant implications for signal transmission