Cellular Neuroscience Exam 2 Flashcards

Q: What is the typical voltage range for a neuron's resting membrane potential (RMP)?

A: Approximately −40 to −90 mV, depending on neuron type.

Q: What ion pumps play a primary role in establishing the RMP?

A: The Na⁺/K⁺ ATPase pumps (Na⁺ out, K⁺ in).

Q: Define a graded (passive) potential

A: A membrane potential change proportional to stimulus magnitude that decays with distance

Q: Define an action potential (AP).

A: A brief (~1 ms), all-or-none active response: rapid depolarization followed by repolarization; amplitude independent of stimulus magnitude

Which ion channels open first during AP initiation?

Voltage-gated Na⁺ channels (fast).

Why do APs not travel backward?

Because of refractoriness: Na⁺ channels are inactivated and K⁺ channels open after an AP, preventing backward firing.

What encodes stimulus intensity in neurons — AP amplitude or frequency?

Frequency of action potentials

What is the function of the axon initial segment (trigger zone)?

High density of Na⁺ channels → lowest threshold for AP initiation; converts graded signals into APs

Q: What is saltatory conduction?

AP propagation in myelinated axons where the AP effectively "jumps" from node to node (nodes of Ranvier).

Q: How does myelin affect conduction velocity?

Myelin increases CV drastically by reducing membrane capacitance and leakage; internodal passive spread is conserved

Q: Compare CV ranges for unmyelinated vs myelinated axons

Unmyelinated: ~0.5-10 m/s; myelinated: up to ~150 m/s

What two factors largely determine electrotonic spread rate?

Axial resistance (r_a) and membrane capacitance (c_m); rate varies inversely with r_a × c_m

Q: Why does increasing axon diameter speed conduction?

A: Larger diameter lowers axial resistance (r_a), improving passive spread

Q: What happens to AP amplitude if you increase the stimulus current above threshold?

A: Amplitude stays the same; increasing current increases firing frequency not amplitude.

Q: What role do voltage-gated K⁺ channels play in AP?

A: They repolarize and often hyperpolarize the membrane after Na⁺ influx; contribute to refractory period

Q: How do intracellular Ca²⁺ levels affect voltage-gated channels?

A: Ca²⁺ can modulate channel probability (e.g., enhance opening of calcium-activated K⁺ channels) and affect excitability.

Q: What do receptor potentials do?

A: Graded potentials produced by sensory transduction; amplitude encodes stimulus intensity and can be converted to AP frequency.

Q: What are synaptic potentials (SPs)?

A: Graded potentials generated across synapses between neurons; can summate at the trigger zone to produce APs.

Q: What is electrotonic conduction?

A: Passive spread of current along the axon with decay over distance (seen in subthreshold responses).

Q: What key structural feature concentrates Na⁺ channels?

A: Nodes of Ranvier

Q: Why are myelinated internodes "insulated"? What's the effect?

Myelin increases membrane resistance and lowers capacitance → reduces current leakage and preserves potential for long distances.

Q: What is the consequence of demyelination on AP propagation?

A: Slower conduction and possible conduction failure because internodal current leaks and fails to bring next node to threshold.

Q: Give two mechanisms that can modulate voltage-gated channel activity.

A: Intracellular Ca²⁺ and neurotransmitters/second-messenger pathways

How do APs differ when evoked by two large depolarizing currents?

They produce identical APs (same amplitude) because of all-or-none behavior

Where does passive current spread occur more effectively: myelinated internodes or unmyelinated axon?

Myelinated internodes (because insulation prevents leak)

Define membrane potential (Vm).

Vm= Vin - Vout

Q: Typical RMP of a neuron?

−60 to −70 mV.

Q: Major ions inside vs outside the cell?

Inside → K⁺, A⁻; Outside → Na⁺, Cl⁻

Q: What maintains the RMP?

Na⁺/K⁺ ATPase and K⁺ leak channels.

Define depolarization and hyperpolarization.

Depolarization = less negative; Hyperpolarization = more negative than rest.

Q: What are electrotonic potentials?

Small graded changes that decay with distance; do not trigger APs.

If membrane permeable only to K⁺, Vm ≈ ?

E_K ≈ −75 mV

What technique allows control of Vm to measure ionic currents?

Voltage clamp.

What did Hodgkin & Katz find when [Na⁺]ₒ was reduced?

AP amplitude decreased → Na⁺ responsible for depolarization.

Two ionic currents in voltage-clamp depolarization?

Early inward (Na⁺) and late outward (K⁺).

Drugs to isolate each current?

TTX blocks Na⁺; TEA blocks K⁺.

Q: What happens if Vm > E_Na?

Na⁺ flows out (outward current).

Q: Goldman equation significance?

Predicts Vm when > one ion is permeable (more realistic than Nernst).

Q: Which ion's permeability dominates at rest?

A: K⁺

Q: Sequence of conductance changes during AP?

A: gNa rises → inactivates → gK rises → repolarization.

What produces the refractory period?

Na⁺ channel inactivation and delayed K⁺ conductance.

Positive feedback loop in AP?

Depolarization → ↑gNa → ↑Na⁺ influx → further depolarization.

Negative feedback loop in AP?

Depolarization → ↑gK → K⁺ efflux → repolarization

Q: Main difference between ion channel and pump?

A: Channels = passive, fast; pumps = active, ATP-driven, slow.

Q: What drives ion flux?

Combined chemical and electrical ( electrochemical ) gradients.

Q: Why do ions need channels?

A: They're hydrated and can't cross the hydrophobic lipid bilayer.

Q: Which ion has a larger hydration shell, Na⁺ or K⁺?

A: Na⁺ → smaller ion, stronger field, larger hydration shell.

Q: Technique for measuring single-channel currents?

A: Patch clamp (Neher & Sakmann).

Q: Patch clamp vs voltage clamp?

A: Patch clamp → single channel; voltage clamp → whole cell (macroscopic).

What does Ohm's law describe in channels?

Linear relationship between current (I) and voltage (V).

Rectifying channels exhibit what type of I-V relationship?

Non-linear; conductance varies with voltage

List three channel gating types.

Voltage, ligand, phosphorylation (+ mechanical).

What blocks nAChR competitively?

Curare (reversible) and α-bungarotoxin (irreversible).

What family includes ACh, GABA, glycine, serotonin receptors?

Ligand-gated ion channels with 5 subunits, 4 TM each

Voltage-gated channel motif?

6 TM segments (S1-S6) + P-region (selectivity filter)

Gap junction structure?

2 connexons (6 connexins each) = 12 subunits total.

K⁺ channels are most numerous and diverse — T/F?

True

Na⁺ channel kinetics vs K⁺?

Na⁺ → fast open/inactivate; K⁺ → slow open, no quick inactivation

Effect of α-toxins on Na⁺ channels?

Slow inactivation → longer AP.

Effect of β-toxins?

Shift activation to more negative Vm → uncontrolled AP firing.

Na⁺/K⁺ pump stoichiometry?

3 Na⁺ out, 2 K⁺ in → electrogenic.

Q: Main function of Ca²⁺ ATPases?

Remove cytosolic Ca²⁺ (PMCA, SERCA).

Na⁺/Ca²⁺ exchanger role?

Expels Ca²⁺ using Na⁺ gradient energy

Q: What connects two neurons in an electrical synapse?

A: Gap junctions (protein channels forming direct cytoplasmic connections).

Q: Which synapse type is faster: electrical or chemical?

A: Electrical synapses are faster (virtually instantaneous transmission).

Name the three criteria to define a neurotransmitter

Present in presynaptic terminal; released Ca²⁺-dependently after depolarization; has specific postsynaptic receptors

Q: Give two examples of small-molecule neurotransmitters.

A: Acetylcholine (ACh), glutamate, GABA, dopamine, serotonin, etc

Q: How are neuropeptides synthesized and transported?

A: Synthesized in soma, packaged into dense-core vesicles, transported by fast axonal transport.

Q: What are MEPPs?

A: Miniature end-plate potentials — spontaneous small postsynaptic potentials at the NMJ.

Q: What experimental evidence supports quantal release?

A: Discrete MEPPs, quantized EPP amplitude distributions, vesicles with high NT concentration, EM showing vesicle fusion

Q: What ion triggers neurotransmitter release from presynaptic terminals?

A: Calcium (Ca²⁺) influx through voltage-gated Ca²⁺ channels

Q: Which vesicle type is docked near the membrane and released with low-frequency stimulation?

A: Small clear-core vesicles (contain small-molecule NTs)

Q: Which kinase phosphorylates synapsin to mobilize reserve vesicles?

Ca²⁺/calmodulin-dependent protein kinase II (CaMKII).

Name the three core SNARE proteins and their locations

Synaptobrevin (vesicle), syntaxin (plasma membrane), SNAP-25 (plasma membrane).

What is the Ca²⁺ sensor that triggers fusion?

Synaptotagmin

How do NSF and SNAPs function?

NSF (ATPase) and SNAPs regulate SNARE assembly/priming for membrane fusion.

Q: Botulinum toxin cleaves what type of protein?

A: SNARE proteins (blocks neurotransmitter release).

Q: Tetanus toxin causes what clinical effect, and how?

A: Spastic paralysis by cleaving SNAREs in inhibitory interneurons → loss of inhibition

Q: What does α-latrotoxin do?

Causes massive NT release (even without extracellular Ca²⁺) via binding neurexins/CL-1

Ionotropic receptors produce what kind of postsynaptic response?

Fast, short-lasting (ms) postsynaptic potentials via direct ion channel opening

Q: Metabotropic receptors work through what mechanism?

G-protein-coupled signaling cascades → slow, longer-lasting modulation

Q: Can one NT bind both ionotropic and metabotropic receptors?

Yes — producing both fast and slow PSPs at the same synapse.

Q: What determines EPC amplitude at the NMJ?

A: Number of channels opened by ACh (g) and driving force (Vm − Erev)

Q: What is a reversal potential?

A: The membrane potential where net current through the open channels is zero (inward/outward current reverses).

Q: Describe the major pathways for neurotransmitter removal.

A: Reuptake, enzymatic degradation, diffusion.

Q: What is synaptic plasticity in the context of synapses?

A: Activity-dependent strengthening or weakening of synaptic efficacy (changes in transmitter release, receptor properties, etc.).

What imaging/evidence supports vesicle recycling?

HRP labeling, fluorescent labeling, freeze-fracture EM showing fusion and endocytosis.

Q: Define cotransmitters

A: Two or more transmitters released from the same neuron (often a small-molecule NT + a neuropeptide).

Q: Why do neuropeptides require high-frequency stimulation for release?

A: Dense-core vesicles are not docked at active zone and need larger or more prolonged Ca²⁺ signals to trigger fusion

What is an end-plate current (EPC)?

The macroscopic current from the summed opening of many ACh receptor channels at the NMJ.

Q: Which ion movements dominate EPC at negative potentials?

A: Na⁺ inward current dominates at negative Vm; at ~0 mV Na⁺ influx balances K⁺ efflux.

What role does actin play in vesicle mobilization?

Vesicles are tethered to actin via synapsin in the reserve pool; phosphorylation releases them for movement.

Q: How do changes in ion gradients affect reversal potentials?

A: Altering ion concentrations shifts equilibrium potentials, thereby shifting E_rev and changing EPC amplitude/polarity.

Name two mechanisms that prime vesicles for fusion

Action of NSF and SNAPs, and SNARE complex assembly (priming organizes SNAREs into fusion-ready conformation)

Q: What experimental manipulation reduces EPP magnitude to MEPP-like amplitudes?

Lowering extracellular Ca²⁺ concentration (reduces vesicle release probability).

Action Potential

An all-or-none active response independent of stimulus amplitude.

Rapid Depolarizing Phase

Caused by the opening of voltage-gated Na⁺ channels.

Saltatory Conduction

Occurs because myelin insulates internodes and APs are regenerated at nodes.

Conduction Velocity

Increased most effectively by myelination.

Refractoriness

Due to Na⁺ channel inactivation and K⁺ channel opening.