Lecture 17 – Electrical Signals, Nerve Cells & Synapses

Announcements & Course Logistics

• Quiz 12 due Wednesday; the lowest quiz score will be dropped when totals are compiled.

• Discussion focus this week: The Kidney.

• Course evaluations earn 5 extra-credit points – complete them online.

• Q & A: Friday, $20\,\text{June}$, $9{:}30{-}11{:}30$ am in $1230\,\text{USB}$.

• Zoom office hours: Sunday, $22\,\text{June}$ at $7\,\text{pm}$.

• Exam 3: Monday, $23\,\text{June}$, $8{-}10\,\text{am}$; covers Lectures 13-18 & Discussions 8-10.

Key Vocabulary

• Na(^+)–K(^+) ATPase (sodium-potassium pump)

  • Integral membrane protein that maintains ion gradients.

• K(^+) leak channels

  • Constitutively open channels allowing K(^+) efflux.

• Voltage-gated Na(^+) channel & Voltage-gated K(^+) channel

  • Constitutively open channels allowing K(^+) efflux.

• Membrane potential, depolarization, repolarization, hyperpolarization, refractory period

• Microenvironment (charged layers at inner & outer leaflets)

• Neuron anatomy: dendrites, cell body (soma), axon, axon hillock, axon terminal

• Myelination, Schwann cell, node of Ranvier

• Pre-/post-synaptic cell, synapse (chemical vs. electrical)

• EPSP, IPSP (excitatory / inhibitory postsynaptic potential)

Learning Objectives (road-map)

• Identify dendrite vs. soma vs. axon functions.

• Explain how the resting membrane potential is built.

• Describe every phase of an action potential (AP) and what ion movement drives it.

• Relate myelin to conduction speed (saltatory propagation).

• Distinguish chemical from electrical synapses & define pre-/post-synaptic.

• Predict whether a post-synaptic cell depolarizes or hyperpolarizes given a mix of inputs.

Nervous System Overview

• Central Nervous System (CNS) = brain + spinal cord → integrates sensory input.

• Peripheral Nervous System (PNS) = all neural tissue outside CNS (sensory neurons, motor pathways, nerves).

• Nerve: bundle of axons + blood vessels + connective tissue.

Flow of Information

1. Sensory neuron converts external stimulus → electrical signal.

2. Interneuron integrates multiple signals, decides output.

3. Motor (effector) neuron sends APs to effector cells (muscle, endocrine, etc.).

• Electrical signals depend on ion movement across plasma membranes, giving rapid & precise communication.

Neuron Anatomy & Signal Path

• Dendrites + soma: receive thousands of inputs (chemical & electrical).

• Axon hillock: sums incoming graded potentials; fires AP if threshold reached.

• Axon: conducts AP to terminals (can be >1 m long).

• Axon terminal: converts electrical signal → neurotransmitter release → new signal in next cell.

Resting Membrane Potential (RMP)

• Typical neuron RMP ≈ $-70\text{ to }-80\,\text{mV}$ (inside negative).

• Ionic asymmetry:
  • Outside: high $[\text{Na}^+]$ (~$145\,\text{mM}$), low $[\text{K}^+]$ (~$5\,\text{mM}$), high $[\text{Cl}^-]$ (~$110\,\text{mM}$).
  • Inside: low $[\text{Na}^+]$ (~$10\,\text{mM}$), high $[\text{K}^+]$ (~$140\,\text{mM}$), low $[\text{Cl}^-]$ (~$10\,\text{mM}$), many fixed protein anions $(-)$.

Establishing RMP: Pumps & Leak Channels

• Na(^+)–K(^+) ATPase expends $1\,\text{ATP}$ → pumps $3\,\text{Na}^+$ out, $2\,\text{K}^+$ in.

• Generates both chemical gradients & a small electrogenic effect (net $+1$ out per cycle).

• K(^+) leak channels: K(^+) diffuses OUT (down its conc. gradient) leaving excess negative charge inside → chief contributor to negative RMP.

• Microenvironment: charges concentrate right along inner/outer leaflets; bulk solutions remain electrically neutral.

• Equilibrium reached when $\Delta G<em>{\text{chemical}}$ (K(^+) out) = $\Delta G</em>{\text{electrical}}$ (K(^+) in) → Nernst potential near $-70\,\text{mV}$ for K(^+).

Action Potential (AP) – All-or-None Electrical Pulse

Phases & Ion Movements

1. Resting state (RMP)

   • V-gated Na(^+)/K(^+) channels closed; only leak channels open.

2. Depolarization

   • Stimulus reaches threshold (~$-55\,\text{mV}$).

   • Voltage-gated Na(^+) channels open → massive $\text{Na}^+$ influx.

   • Membrane potential rises toward $+40\,\text{mV}$.

3. Repolarization

   • V-gated Na(^+) channels inactivate (refractory state).

   • V-gated K(^+) channels open → $\text{K}^+$ efflux restores negativity.

4. Hyperpolarization (undershoot)

   • K(^+) channels remain open briefly; Vm dips below RMP.

5. Return to RMP

   • V-gated K(^+) channels close; leak channels + Na(^+)–K(^+) ATPase re-establish resting state.

• Entire sequence takes milliseconds and has fixed amplitude (binary).

Voltage-Gated Channel Conformations

• V-gated Na(^+) channel: 3 states
  • Closed (resting; voltage-sensitive)
  • Open (activated)
  • Inactivated (refractory; not reopened by depolarization)

• Absolute refractory period: no new AP because Na(^+) channels inactivated.

• Relative refractory period: hyperpolarization phase; stronger stimulus can fire AP.

Propagation of the AP

• Local influx of $\text{Na}^+$ creates positive charge → depolarizes adjacent membrane → opens the next set of Na(^+) channels (positive feedback).

• Refractory region behind prevents back-propagation → one-way travel from hillock to terminals.

Myelination & Saltatory Conduction

• Schwann cells (PNS) or oligodendrocytes (CNS) wrap axon with myelin (lipid insulation).

• Ion channels are sparse under myelin, densely clustered at nodes of Ranvier.

• Current travels internally under sheath with minimal leak, then “recharges” at next node → AP appears to jump (saltatory) → speeds up conduction 10–100× & reduces energetic cost (pumps only at nodes).

• Demyelination (e.g., Multiple Sclerosis):
  • Leaky axons, slowed or failed conduction.
  • Neurons expend more ATP to maintain Vm → metabolic stress & neuro-degeneration.

Synapses – Passing the Signal

• Electrical synapse (gap junction): direct cytoplasmic continuity; rare; near-instantaneous.

• Chemical synapse (dominant): uses neurotransmitter.
  • Presynaptic cell → synaptic cleft (~$20\,\text{nm}$) → postsynaptic cell.

Steps of Neurotransmitter Release (Chemical Synapse)

1. AP arrives at axon terminal.

2. Depolarization opens voltage-gated Ca(^{2+}) channels.

3. $\text{Ca}^{2+}$ influx (down electrochemical gradient).

4. $[\text{Ca}^{2+}]_{\text{in}}$ rises; binds vesicle-fusion proteins (SNAREs).

5. Synaptic vesicles fuse → exocytosis of neurotransmitter into cleft.

Postsynaptic Actions

• Neurotransmitter binds ligand-gated (neurotransmitter-gated) ion channels → alters Vm.
  • Excitatory transmitters (e.g., glutamate, acetylcholine) open Na(^+) or non-selective cation channels → depolarization → EPSP.
  • Inhibitory transmitters (e.g., GABA, glycine) open Cl(^{-}) or K(^+) channels → hyperpolarization → IPSP.

• EPSPs & IPSPs are graded; amplitude ∝ amount of transmitter & receptor number.

Summation at the Axon Hillock

• Temporal summation: rapid successive EPSPs from one synapse add up.

• Spatial summation: EPSPs from multiple synapses combine.

• Cancellation: simultaneous EPSP + IPSP may neutralize.

• Threshold reached → new AP; threshold not reached → no firing.

Neurotransmitter Clearance

• Enzymatic degradation (e.g., acetylcholinesterase breaks down acetylcholine).

• Reuptake into presynaptic terminal.

• Diffusion away.

Clinical & Real-World Connections

• Acetylcholine at neuromuscular junction: obligatory excitatory transmitter for skeletal muscle; removal by acetylcholinesterase terminates contraction.

• Botulinum toxin (Botox)
  • Bacterial protease that cleaves SNARE proteins.
  • Blocks vesicle fusion → prevents acetylcholine release → flaccid paralysis of facial muscles → decreases wrinkle formation.

• Multiple Sclerosis (MS)
  • Autoimmune demyelination → slowed conduction, muscle weakness, coordination issues.

Concept Checks / Sample Questions

• Opening an extra Na(^+) channel at rest would decrease (collapse) the membrane potential (drive Vm toward $0\,\text{mV}$).

• Predict what happens to K(^+) distribution when the charge gradient collapses: K(^+) leaves cell until new equilibrium reached.

Key Numbers & Equations

• Sodium–potassium pump stoichiometry: $3\,\text{Na}^+<em>{\text{out}} \; / \; 2\,\text{K}^+</em>{\text{in}}$ per ATP.

• Resting potential: $V_m \approx -70\,\text{mV}$.

• Threshold potential: $\sim -55\,\text{mV}$.

• AP peak: $+40\,\text{mV}$.

• Time course of AP: a few ms.

• Conduction velocity: unmyelinated $\approx 1\text{–}10\,\text{m/s}$; myelinated up to $100\,\text{m/s}$.

Ethical / Practical Implications

• Understanding ion channel pharmacology underlies treatment of epilepsy, pain, arrhythmia.

• Insights into demyelinating diseases guide development of remyelination therapies.

• Neurotoxin mechanisms (Botox) exploited for both medical (spasticity, migraines) and cosmetic purposes – raises questions about safety, regulation, and equity of access.

Concept Map – Putting It All Together

• Na(^+)–K(^+) ATPase & leak channels → RMP → voltage-gated channels → AP → myelination speeds AP → AP arrives at terminal → $\text{Ca}^{2+}$-triggered neurotransmitter release → ligand-gated channels in next neuron → graded EPSPs/IPSPs → summation at hillock → new AP or silence.