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Neurons and Glia, Membrane Potential, Action Potential, and Synaptic Transmission
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What are the two major cellular components of nervous tissue?
Neurons + glia.
Main functions of neurons?
Sense changes, process information, communicate with neurons, command responses.
Main general functions of glia?
Insulate, support, nourish, and regulate the environment of neurons.
Gray matter
Neurons and glia.
White matter
Primarily myelinated axons.
What are neurites?
Axons + dendrites.
CNS
Brain + spinal cord.
PNS
Nerves outside the CNS carrying signals to/from CNS.
Afferent vs efferent
Afferent ARRIVES at CNS (sensory); efferent EXITS CNS (motor).
Typical direction of neuronal information flow
Dendrites/soma → axon → axon terminal.
Dendrite main role
Receives synaptic input.
Axon main role
Conducts signals away from soma toward terminals.
Anterograde axonal transport
Soma → terminal; kinesin.
Retrograde axonal transport
Terminal → soma; dynein.
What structures serve as tracks for axonal transport?
Microtubules.
If retrograde transport fails but anterograde works, likely motor affected?
Dynein.
If both anterograde and retrograde transport fail, likely structure affected?
Microtubules.
Astrocyte functions
BBB support, extracellular K+/NT regulation, neurite growth/support.
Which glia perform spatial buffering of extracellular K+?
Astrocytes.
Which glia contribute to the blood-brain barrier?
Astrocytes.
Oligodendrocytes
Myelinate CNS axons; one cell can myelinate several axons.
Schwann cells
Myelinate PNS axons; one cell myelinates one axonal segment.
Oligodendrocyte vs Schwann
Oligodendrocyte = CNS/multiple axons; Schwann = PNS/single axon segment.
Microglia
Phagocytose/remove debris from dead or dying cells.
Ependymal cells
Line the brain's fluid-filled ventricles.
Node of Ranvier
Exposed axonal membrane between myelinated segments.
Nissl stain
Stains somas/nucleic acids, especially RNA on rough ER; stains all somas.
Golgi stain
Stains a small percentage of neurons but stains each selected neuron in its entirety.
Reticular theory
Golgi: neurons form a continuous interconnected network.
Neuron doctrine
Cajal: neurons are discrete individual cells.
Why was Golgi stain useful to Cajal?
It revealed entire individual neurons and their processes.
Leak channel
Passive/always open.
What do gated channels do?
Opens/closes in response to a stimulus.
What can affect gate channels?
Voltage, ligand, phosphorylation, mechanical force, or light.
Resting membrane potential
Voltage across membrane at rest; inside is negative relative to outside.
What two forces determine ion movement?
Chemical + electrical forces.
Chemical force
Concentration gradient drives ions high → low concentration.
Electrical force
Attraction/repulsion determined by ion charge and membrane voltage.
Electrochemical gradient
Combined chemical + electrical forces.
For Na+ at normal resting Vm, what is the chemical force direction?
IN.
For Na+ at normal resting Vm, electrical force direction?
IN.
For K+ at normal resting Vm, chemical force direction?
OUT.
For K+ at normal resting Vm, what is the ELECTRICAL force direction?
IN.
Equilibrium potential (Eion)
Vm where electrical and chemical forces balance → no NET movement of that ion.
What does the Nernst equation calculate?
Equilibrium potential for ONE ion.
What does z represent in Nernst?
Ion's charge/valence.
Driving force equation
Driving force = Vm − Eion.
What does driving-force magnitude tell you?
Strength of the push on the ion/current.
When is driving force zero?
Vm = Eion.
Can an open channel have zero net ion flow?
Yes; if Vm = Eion/Erev, driving force is zero.
What does every ion tend to do to Vm?
Pull Vm toward its own equilibrium potential.
If [ion] is equal inside/outside, what is its Eion?
0 mV.
If concentrations are equal but Vm ≠ 0, can the ion move?
Yes; electrical force can still drive it.
If multiple ions are permeable, what determines Vm?
Relative permeability/conductance and equilibrium potentials.
At rest, why is Vm closer to EK than ENa?
Resting membrane is much more permeable to K+.
Current equation
Iion = gion(Vm − Eion).
What is Conductance (g)?
How readily ions flow; increases with more open relevant channels.
Conductance vs driving force
g = channel availability; DF = Vm − Eion.
What does the Na+/K+ pump move?
3 Na+ OUT + 2 K+ IN per ATP.
Main role of Na+/K+ pump
Maintains Na+ and K+ concentration gradients.
If only ONE ion is permeable, where does Vm settle?
At that ion's Eion.
If only one ion is permeable, does changing its conductance change final Vm?
No; final Vm remains at that ion's Eion.
Adding a new ion conductance does what to Vm?
Pulls Vm toward the new ion's Eion.
Increasing extracellular K+ usually does what to resting Vm?
Depolarizes it by making EK less negative.
Voltage clamp
Controls Vm and measures resulting ionic current.
Current clamp
Controls injected current and measures changes in Vm.
Why is voltage clamp useful?
Holds driving force fixed so current changes can reveal conductance changes.
Depolarization
Vm becomes more positive.
Hyperpolarization
Vm becomes more negative.
Threshold
Critical Vm where regenerative AP mechanisms take off.
Action potential rule
All-or-none once threshold is reached.
Does stronger stimulation increase AP amplitude?
No; it increases AP frequency, not individual AP amplitude.
What leads to AP rising phase?
VG Na+ channels open → Na+ influx → rapid depolarization.
Why is AP rise positive feedback?
Depolarization opens Na+ channels → Na+ influx causes more depolarization.
What is the AP falling/repolarizing phase caused by?
Na+ channels inactivate + delayed VG K+ channels open → K+ exits.
AP undershoot
VG K+ channels close slowly → continued elevated K+ conductance.
VG Na+ channel special feature
Fast activation followed by inactivation gate.
VG K+ channel timing
Opens more slowly after depolarization and closes slowly.
Which changes rapidly during an AP: Vm or ENa?
Vm; ENa is essentially unchanged over one AP.
At AP overshoot, which ion has especially large DF?
K+, because Vm is far from EK.
At undershoot, which ion has especially large DF?
Na+, because Vm is far from ENa.
Large driving force means large conductance?
NO. They are separate variables.
TTX
Blocks voltage-gated Na+ channels/current.
TEA
Blocks voltage-gated K+ channels/current.
TTX during voltage clamp removes what?
Early inward Na+ current; K+ current remains.
TEA during voltage clamp removes what?
Late outward K+ current; Na+ current remains.
Why does Na+ current disappear during sustained voltage clamp?
Na+ channels inactivate → gNa falls despite constant Vm.
Why can K+ current persist during voltage clamp?
K+ channels lack rapid Na-like inactivation.
At Vm = ENa, what happens to Na+ current?
Zero net Na+ current even if Na+ channels are open.
What happens to Na+ current if Vm rises above ENa?
It reverses direction and becomes outward.
Absolute refractory period
Na+ channels are inactivated → another AP cannot occur.
Relative refractory period
Na+ channels recovered but K+ conductance/hyperpolarization remains → stronger stimulus required.
Why does an AP normally propagate only forward?
Membrane behind AP is refractory due to Na+ channel inactivation.
What happens if AP is artificially initiated in the middle of excitable axon?
It can propagate in BOTH directions.
Saltatory conduction
AP regeneration at nodes of Ranvier in myelinated axons.
Why does myelin increase conduction velocity?
↑ membrane resistance → less current leak → depolarization spreads farther.
Effect of demyelination
More current leaks → conduction slows or can fail.
Effect of increasing axon diameter
↓ internal resistance → faster conduction.
Membrane resistance Rm
Resistance to current leaking OUT through membrane.
Internal resistance Ri
Resistance to longitudinal current flow INSIDE cell.