Cellular Neurobiology: Neurons, Action Potentials, and Synaptic Transmission

Comprehensive practice flashcards on neuron cell biology, membrane biophysics, action potential propagation, synaptic ultrastructure, and mechanisms of short-term synaptic plasticity.

Selectivity Filter of Potassium Channel

A narrow $1.96\,\text{Å}$ pore region containing backbone carbonyl oxygens positioned precisely to coordinate an unhydrated $K^+$ ion (naked radius $1.38\,\text{Å}$), replacing its hydration shell and facilitating rapid permeation.

Selectivity Filter of Sodium Channel

A pore opening measuring $2.66\,\text{Å}$ in diameter that is wide enough to permit passage of a partially hydrated $Na^+$ ion (naked radius $1.02\,\text{Å}$) while sterically excluding hydrated $K^+$ ions.

Waters of Hydration

The electrostatic shell of water molecules surrounding an ion in solution, which must be energetically shed for an ion to pass through narrow channel filters.

Dehydration Energetics (Selectivity Filter)

The thermodynamic requirement that an ion interact tightly with coordinating amino acid charges to offset the energetic penalty of shedding bound water; $Na^+$ cannot pass through a $K^+$ channel because it is too small to interact simultaneously with both walls of the wider filter to lose its hydration shell.

Structural Stereotypy vs. Neuronal Morphological Diversity

The cell biological contrast between organs like the liver, which have a few cell types and repeating stereotyped structures, and nervous tissue, which contains a vast diversity of neuronal shapes and sizes specialized for information transfer.

Proximal Tubule Epithelium

Kidney transport cells that establish an osmotic gradient using $Na^+/K^+$ pumps, water channels, and organic anion (OA) and organic cation (OC) transporters to recover water and solutes before urine is released.

Neuroglia (Glial Cells)

Non-electrically excitable support cells in nervous tissue that nourish neurons, electrically insulate axons, and maintain extracellular homeostasis while possessing a negative resting membrane potential.

Astrocytes

Glial cells whose foot processes wrap around brain capillaries to induce tight junction formation, support the blood-brain barrier, and regulate local neurochemistry.

Blood-Brain Barrier (BBB)

A protective physiological barrier formed by capillary endothelial cells linked by tight junctions and surrounded by astrocyte foot processes, limiting pathogen entry and chemical fluctuations while impeding therapeutic drug delivery.

Intranasal Drug Delivery Route

A non-invasive method that bypasses the blood-brain barrier by administering therapeutics through the nasal cavity to access the brain directly via olfactory and trigeminal nerve pathways.

Receptor-Mediated Transcytosis (BBB Shuttles)

A targeted drug delivery strategy using bispecific antibodies or ligands that bind to endogenous endothelial receptors, such as the Transferrin Receptor 1 (TfR1), to cross into the brain via endocytosis and exocytosis.

Focused Ultrasound (FUS)

An MRI-guided technique using focused sound waves and intravenous microbubbles to transiently and locally open endothelial tight junctions in the brain without permanent tissue damage.

Oligodendrocytes

Glial cells of the central nervous system that wrap multi-layered myelin sheaths around multiple axonal segments.

Schwann Cells

Glial cells of the peripheral nervous system that form concentric myelin wraps around single axonal internodes.

Myelin Sheath

Multi-layered lipid membranes lacking ion channels wrapped around axons by glia that increase action potential conduction velocity and reduce the metabolic energy needed to maintain ion gradients.

Multiple Sclerosis (MS)

An autoimmune disorder characterized by inflammatory demyelination and glial scarring (sclerosis) in central white matter tracts, causing conduction delays and eventual impulse failure.

Microglia

Resident phagocytic cells of the central nervous system that dynamically survey brain tissue and engulf cellular debris and pathogens.

G-Actin (Globular Actin)

A monomeric cytoskeletal protein measuring approximately $5\,\text{nm}$ that binds ATP and polymerizes to assemble filamentous actin strands.

F-Actin (Filamentous Actin)

A polarized helical actin polymer measuring $\sim 7\,\text{nm}$ in width with a $\sim 35\,\text{nm}$ helical crossover repeat, possessing distinct fast-growing plus (+$) and slow-growing minus (-$$) ends.

Actin Treadmilling

A dynamic steady-state process where ATP-bound G-actin monomers continuously add to the plus (+$) end while ADP-actin subunits disassemble from the minus (-$$) end of an actin filament.

Neuronal Growth Cone

A specialized motile structure at the leading tip of an extending neurite containing a central domain, an actin arc transition zone, and a peripheral domain that directs axonal pathfinding.

Filopodia

Slender, finger-like sensory protrusions in the growth cone peripheral domain formed by parallel bundles of linear actin filaments.

Lamellipodia

Broad, sheet-like motile extensions of the growth cone peripheral domain composed of a cross-linked branched actin filament gel network.

Arp2/3 Complex

A protein complex that binds existing actin filaments and nucleates daughter filament branches at a characteristic $70^{\circ}$ angle.

ADF/Cofilin

An actin-severing and depolymerizing protein that binds to ADP-actin subunits to accelerate filament disassembly at the minus ($-$) end.

Profilin

An actin-binding protein that catalyzes ADP-to-ATP nucleotide exchange on monomeric G-actin, recharging monomers for incorporation into filament plus ($$+$) ends.

Soma (Cell Body)

The metabolic center of a neuron housing the nucleus and major organelles, where incoming electrical and biochemical signals are integrated.

Dendrites

Branched neuronal arborizations specialized to receive synaptic inputs from other neurons, often bearing specialized dendritic spines.

Axon Hillock

The specialized, cone-shaped region of the neuronal soma where the axon originates, containing a high density of voltage-gated $Na^+$ channels for action potential initiation.

Sodium-Potassium Pump ($Na^+/K^+$ ATPase)

An electrogenic primary active transporter that hydrolyzes ATP to export $3\,Na^+$ ions and import $2\,K^+$ ions against their concentration gradients.

Squid Giant Axon Model (Loligo)

A classic neurobiological model organism whose giant axon enabled the experimental determination of ion concentrations, conductances, and action potential biophysics.

Intracellular vs. Extracellular Ion Ratios

The biophysical principle stating that membrane potential is governed by the relative ratio of internal to external ion concentrations ($K^+$ ratio is $20:1$ in squid, $28:1$ in mammal) rather than absolute quantities.

Potassium Equilibrium Potential ($E_K$)

The theoretical membrane voltage ($\approx -90\,\text{mV}$ in mammals) at which the outward concentration gradient for $K^+$ is precisely balanced by the inward electrical attractive force.

Sodium Equilibrium Potential ($E_{Na}$)

The theoretical membrane potential ($\approx +60\,\text{mV}$ in mammals) at which the inward chemical driving force for $Na^+$ is balanced by positive intracellular electrostatic repulsion.

Resting Membrane Potential ($V_{\text{rest}}$)

The baseline electrical potential difference across the plasma membrane of an unstimulated cell, typically ranging between $-55\,\text{mV}$ and $-70\,\text{mV}$.

Goldman-Hodgkin-Katz (GHK) Equation

A mathematical formula ($V_{\text{rest}} \approx 62 \cdot \log\left(\frac{P_K[K^+]_o + P_{Na}[Na^+]_o}{P_K[K^+]_i + P_{Na}[Na^+]_i}\right)$) that calculates resting membrane potential by accounting for concentration gradients and relative ion permeabilities.

Potassium Leak Channels

Non-voltage-dependent ion channels open at rest that confer a baseline $K^+$ permeability approximately $20$ times greater than $Na^+$ permeability ($P_K \approx 20 \times P_{Na}$).

Voltage-Gated Sodium Channel

An integral membrane protein that opens rapidly in response to membrane depolarization, producing the inward $Na^+$ current responsible for the action potential rising phase.

Threshold Potential

The membrane potential level ($\approx -55\,\text{mV}$) at which regenerative opening of voltage-gated $Na^+$ channels is triggered, initiating an all-or-none action potential.

Depolarization (Rising Phase)

The rapid phase of an action potential where the membrane potential becomes increasingly positive (peaking at $\approx +30\,\text{mV}$) due to rapid $Na^+$ influx.

Inactivation Loop (Ball-and-Chain Mechanism)

A cytosolic protein domain that swings into the open pore of a voltage-gated $Na^+$ channel shortly after opening, terminating $Na^+$ influx and preventing retrograde impulse propagation.

Repolarization (Falling Phase)

The recovery phase of an action potential driven by the inactivation of voltage-gated $Na^+$ channels and the delayed opening of voltage-gated $K^+$ channels ($K^+$ efflux).

Hyperpolarization (Undershoot)

The transient phase following an action potential where the membrane potential becomes more negative than resting level, approaching $E_K$ ($\approx -90\,\text{mV}$) due to lingering open voltage-gated $K^+$ channels.

Refractory Period

The post-action potential interval during which inactivated voltage-gated $Na^+$ channels prevent or limit the firing of an immediate subsequent impulse.

Tetrodotoxin (TTX)

A marine neurotoxin found in pufferfish and blue-ringed octopuses that selectively occludes voltage-gated sodium channels, abolishing action potential generation.

Saxitoxin (STX)

A potent neurotoxin produced by marine dinoflagellates associated with red tides that blocks voltage-gated sodium channels, causing paralytic poisoning.

Conotoxin

A peptide toxin derived from the venom of predatory cone snails (Conus) that selectively targets and blocks voltage-gated calcium channels at presynaptic terminals.

Electrical Synapse

A direct neuronal junction mediated by gap junctions that allows passive, bidirectional current transfer with negligible synaptic delay.

Connexon

A hexameric hemichannel formed by six transmembrane connexin proteins; two aligned connexons span a $3.5\,\text{nm}$ gap to form a continuous hydrophilic channel.

Chemical Synapse

A junction where an electrical action potential triggers exocytosis of neurotransmitters across a fluid-filled cleft ($15\text{--}20\,\text{nm}$) to bind postsynaptic receptors.

Purkinje Cell

A principal inhibitory neuron of the cerebellar cortex possessing an expansive, planar dendritic tree with over $100,000$ dendritic spines receiving synaptic inputs.

Dendritic Spines

Small bulbous protrusions on dendritic branches that compartmentalize postsynaptic receptors and signaling proteins for individual excitatory synapses.

Synaptic Cleft

The narrow extracellular space measuring approximately $15\text{--}20\,\text{nm}$ between the presynaptic active zone and the postsynaptic membrane at a chemical synapse.

Ionotropic Receptors

Ligand-gated ion channels composed of multiple protein subunits surrounding an ion pore that mediate direct, rapid synaptic transmission on a millisecond timescale.

Nicotinic Acetylcholine Receptor (nAChR)

A pentameric ionotropic receptor (composed of $\alpha_2\beta\gamma\delta$ subunits in muscle) possessing two ACh binding sites that allows cation flux upon activation.

Metabotropic Receptors (GPCRs)

Seven-transmembrane domain receptors lacking an intrinsic pore that signal through heterotrimeric G-proteins to alter ion channels and cellular excitability over seconds to minutes.

Heterotrimeric G-Proteins

Signaling complexes composed of $\alpha$, $\beta$, and $\gamma$ subunits that dissociate into an active GTP-bound $\alpha$ subunit and a $\beta\gamma$ complex upon GPCR stimulation.

Excitatory Postsynaptic Potential (EPSP)

A transient depolarization of the postsynaptic membrane caused by positive ion influx that brings the membrane potential closer to the action potential firing threshold.

Inhibitory Postsynaptic Potential (IPSP)

A hyperpolarizing or stabilizing postsynaptic potential change that prevents the membrane potential from reaching the action potential threshold.

Synaptic Vesicle

A small membrane-enclosed presynaptic organelle loaded with neurotransmitters via proton-dependent antiporters driven by a vacuolar $H^+$ ATPase (V-ATPase).

SNARE Complex

A core fusion machinery consisting of a four-helix bundle formed by synaptobrevin, syntaxin, and SNAP-25 that zippers together to pull vesicle and plasma membranes into close apposition.

Synaptobrevin (VAMP)

A vesicular SNARE (v-SNARE) transmembrane protein integrated into the synaptic vesicle membrane that contributes one alpha-helix to the core SNARE bundle.

Syntaxin

A target SNARE (t-SNARE) integrated into the presynaptic plasma membrane that contributes one alpha-helix to the four-helix SNARE fusion complex.

SNAP-25

A presynaptic plasma-membrane-associated t-SNARE that contributes two alpha-helices to the core four-helix SNARE complex.

Synaptotagmin

A calcium-sensing vesicular protein that, upon binding entering $Ca^{2+}$, alters its membrane-associating properties to trigger immediate membrane fusion and exocytosis.

Vesicle Priming

An ATP-dependent pre-fusion maturation step involving proteins such as Munc-18, Rab3A, and complexin that renders docked vesicles competent for rapid calcium-triggered fusion.

Lambert-Eaton Myasthenic Syndrome (LEMS)

An autoimmune disorder in which autoantibodies attack presynaptic voltage-gated $Ca^{2+}$ channels, reducing calcium influx and neurotransmitter release probability.

Botulinum Neurotoxins (BoNT)

Bacterial zinc-dependent proteases that selectively cleave SNARE proteins (e.g., BoNT-A, C, E cleave SNAP-25; BoNT-B cleaves synaptobrevin), blocking neurotransmitter release.

Latrotoxin

A venom component of black widow spiders that binds presynaptic receptors to trigger massive, uncontrolled vesicle fusion and release independent of calcium.

Active Zone Architecture

A structured macromolecular scaffold at the presynaptic plasma membrane (comprising beams, ribs, and pegs at the frog neuromuscular junction) that aligns vesicles with voltage-gated $Ca^{2+}$ channels.

Clathrin Triskelion

A three-legged pinwheel-shaped protein complex composed of three heavy and three light chains that polymerizes into a polyhedral cage to curve membranes during endocytosis.

Dynamin

A GTPase mechanochemical enzyme that forms a spiral ring around the neck of budding clathrin-coated pits, hydrolyzing GTP to pinch off internalized vesicles.

shibire Mutation

A temperature-sensitive mutation in Drosophila encoding dynamin that arrests endocytosis at $29\,^{\circ}\text{C}$, leading to rapid depletion of synaptic vesicles and paralysis.

Synaptic Plasticity

The physiological capacity of chemical synapses to alter the strength of their connection through presynaptic changes in transmitter release or postsynaptic receptor modifications.

Dopamine Transporter (DAT)

A presynaptic reuptake transporter that terminates dopamine signaling; its inhibition by cocaine causes sustained dopamine accumulation in the synaptic cleft and eventual receptor downregulation.

Crayfish Walking Leg (Appendage Anatomy)

An experimental crustacean preparation comprising the ischiopodite, meropodite, carpopodite, propodite, and dactylopodite used to analyze neuromuscular synaptic transmission.

Synaptic Facilitation

A short-term form of synaptic enhancement where successive presynaptic action potentials produce progressively larger EPSPs due to accumulation of residual $Ca^{2+}$ in the terminal.

Calcium Cooperative Release Rule

The non-linear, fourth-power power-law relationship between presynaptic calcium concentration and neurotransmitter exocytosis ($\text{Release} = k \cdot [Ca^{2+}]^4$, slope $\approx 4$ on a log-log plot).

Habituation (in Aplysia)

A non-associative learning process where repeated benign tactile siphon stimulation causes a progressive reduction in gill withdrawal due to presynaptic depression of sensory neuron transmitter release.

Short-Term Sensitization (in Aplysia)

The enhancement of the gill-withdrawal reflex after a tail shock that stimulates facilitatory interneurons to release serotonin (5-HT), initiating a PKA cascade that broadens sensory action potentials and increases transmitter release.