BIO 105 – Electrical Signaling & Synaptic Physiology

Electrical Signals in Neurons

Overview – “The Wiring & Electricity of the Nervous System”

Neurons use an electro-chemical language to move information rapidly over long anatomical distances and to integrate that information in higher centers (spinal cord & brain).
Conduction speed in the somatic division can reach 280\,\text{mph} \;(\approx 125\,\text{m·s}^{-1}), rivaling high-speed rail lines and underscoring the evolutionary premium placed on fast reflexes.

Membrane Potentials – The Battery Analogy

Ion gradients across the plasma membrane create a charge separation – a miniature battery that can be tapped when channels open.
• Outside: high $\text{Na}^+$ , $\text{Ca}^{2+}$ , $\text{Cl}^-$ (net positive)
• Inside: high $\text{K}^+$ , negatively charged proteins (net negative)
Voltage difference is measured in millivolts (mV).
$Vm = V{\text{inside}} - V_{\text{outside}}$ (convention: inside relative to outside).
Potential Energy (PE): stored energy due to charge separation—“opposites attract.”
Qualitatively $PE = q \Delta V$ (charge × voltage).

Resting Membrane Potential (RMP)

A neuron at rest is polarized: $\text{RMP} \approx -70\,\text{mV}$ .
Maintained by two main players:
1. Gated Channels – mostly closed at rest; they re-establish RMP after each impulse by returning membrane permeability to baseline.
2. Sodium–Potassium Pump (Na⁺/K⁺-ATPase) – active transport using ATP.
 • Exchanges $3\,\text{Na}^+{\text{out}}$ for $2\,\text{K}^+{\text{in}}$ per cycle.
 • Hyperpolarizes the cell slightly and replenishes ionic gradients so the next impulse can occur.

Action Potential (AP) – “The Digital Spike”

All-or-None: once threshold is crossed, the neuron fires fully—comparable to firing a gun; pressing the trigger harder doesn’t create a bigger bullet.
Self-propagating wave that moves without decrement.

Sequence of Ionic Events

Phase	Key Voltage	Ion Movements	Notes
Polarized (rest)	$-70\,\text{mV}$	Leaky $K^+$ out	Stable battery
Threshold	$\approx -55\,\text{mV}$	Voltage-gated $\text{Na}^+$ channels open	“Point of no return”
Depolarization	toward $+30\,\text{mV}$	Massive $\text{Na}^+$ influx	Membrane polarity reverses
Repolarization	falling back to $-70\,\text{mV}$	$\text{Na}^+$ channels inactivate, $\text{K}^+$ channels open, Na⁺/K⁺ pump active	Restores negative interior
Hyperpolarization	< -70\,\text{mV}	Continued $\text{K}^+$ efflux	Produces Relative Refractory

Refractory Periods

Absolute Refractory: From threshold until mid-repolarization; a second AP cannot occur regardless of stimulus – Na⁺ channels are either open or inactivated.
Relative Refractory: Late repolarization/hyperpolarization; a stronger-than-normal stimulus can re-fire an AP because some Na⁺ channels have reset.

Propagation of the Action Potential

Continuous Conduction – domino effect in unmyelinated axons; every spot of membrane depolarizes. Slower and energy-costly.
Saltatory Conduction – AP “leaps” from one Node of Ranvier to the next in myelinated axons, accelerating speed and reducing ATP cost.
• Myelin acts like electrical tape, preventing ion leakage.

Factors That Dictate Conduction Velocity

Myelination ↑ → Velocity ↑.
Axon Diameter ↑ → Internal resistance ↓ → Velocity ↑.

Signal Transmission at Synapses

Structure – The 3-Part Junction

Presynaptic Neuron – sender; terminates in a synaptic bulb/knob containing neurotransmitter (NT)-filled vesicles.
Synaptic Cleft – $\approx 20\,\text{nm}$ extracellular gap.
Postsynaptic Membrane – receptor-laden region of dendrite, soma, or muscle/gland cell.

Chemical Synapse: Step-by-Step Mechanism

AP arrives at presynaptic bulb.
Voltage-gated $\text{Ca}^{2+}$ channels open → $\text{Ca}^{2+}$ influx.
$\text{Ca}^{2+}$ triggers exocytosis: vesicles fuse and discharge NT into cleft.
NT diffuses and binds to specific receptors → ligand-gated channels open/close on postsynaptic cell.
Postsynaptic effect:
• EPSP (Excitatory Postsynaptic Potential) – depolarization (e.g., $\text{Na}^+$ entry).
• IPSP (Inhibitory Postsynaptic Potential) – hyperpolarization (e.g., $\text{Cl}^-$ in, $\text{K}^+$ out).

Clearing the Cleft – “Reset for Next Message”

Diffusion into surrounding interstitial fluid.
Enzymatic Degradation – e.g., acetylcholinesterase (AChE) breaks down ACh in < 1\,\text{ms}.
• Clinical tie-in: AChE inhibitors ↑ ACh (used in myasthenia gravis, Alzheimer’s, some pesticides).
Re-uptake into presynaptic bulb via transporter proteins.
• SSRIs (selective serotonin reuptake inhibitors) block this step for serotonin, elevating mood in depression (Box 19-2).

Neurotransmitters – The Chemical Vocabulary

Small-Molecule NTs

Acetylcholine (ACh)
• Excitatory at skeletal muscle NMJ.
• Inhibitory at cardiac muscle (slows heart rate via vagus nerve).
Amines (Biogenic Amines) – largely CNS:
• Serotonin (5-HT) – mood, appetite, sleep, temperature, and sensory perception.
• Dopamine (DA) – emotion, reward, addiction, motor tone (degeneration → Parkinson’s).
• Epinephrine (E) - Involved in the fight-or-flight response, increasing heart rate, blood pressure, and energy availability.
Norepinephrine (NE) - Modulates attention, arousal, and response to stress, playing a crucial role in sleep-wake cycles and the sympathetic nervous system's responses.
Amino Acids – glutamate (major excitatory), GABA & glycine (major inhibitory), aspartate.
Nitric Oxide (NO) – gaseous NT; diffuses directly through membranes; potent vasodilator (e.g., penile erection, cerebral blood flow).

Neuropeptides – “Neuromodulators” (3–40 amino acids)

Enkephalins & Endorphins – endogenous opioids; analgesia, euphoria (“runner’s high”).
Substance P – intensifies pain perception.

Synapses & Memory – "Neurons that Fire Together, Wire Together"

Short-Term Memory (STM, sec or min): likely due to transient facilitation/inhibition at existing synapses (more NT release, Ca²⁺ buildup, receptor phosphorylation).
Long-Term Memory (LTM, months or years): requires structural remodeling—new dendritic spines, more synapses, altered gene expression ("protein synthesis step").
Hebbian plasticity: repeated activation strengthens selected circuits; unused connections may be pruned ("use it or lose it").

Complexity in Neural Networks (Box 19-3)

The CNS operates through divergent, convergent, reverberating, and parallel-after-discharge circuits, enabling integration, pattern recognition, and redundancy.
Visualizing these networks helps illustrate how localized lesions yield specific deficits (clinical neuroanatomy).

Disorders of Neural Signaling

Parkinson’s disease - a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra, leading to motor symptoms such as tremors, rigidity, bradykinesia, and postural instability.
Alzheimer’s disease - a chronic neurodegenerative condition associated with progressive cognitive decline, memory loss, and behavioral changes as a result of the accumulation of amyloid plaques and tau tangles.
Huntington’s disease - a genetic disorder caused by the degeneration of neurons in the basal ganglia, resulting in uncontrolled movements, emotional disturbances, and cognitive decline.

Conduction (Myelin & Axons)

Multiple Sclerosis (MS) – autoimmune demyelination → slowed/blocked APs; symptoms vary (vision loss, muscle weakness). Ethical issue: access to disease-modifying therapies.
Nerve Damage – trauma, toxins, metabolic (e.g., diabetic neuropathy) sever axons; Wallerian degeneration can follow.
Cerebrovascular Accident (CVA, Stroke) – Ischemia, due to reduced $\text{O}_2$ and glucose, results in energy failure, which causes ion pump collapse, excitotoxicity, and ultimately neuronal death.

Synaptic Pathology

Myasthenia Gravis (MG) – antibodies block/destroy nicotinic ACh receptors at skeletal NMJ → fluctuating muscle weakness; treated with AChE inhibitors, immunotherapy.
Autism Spectrum Disorder (ASD) – emerging evidence of altered synapse number/function and excitatory/inhibitory imbalance; complex genetics & environmental interactions.

Quick-Reference Q & A (Exam Style)

What voltage defines the RMP? $-70\,\text{mV}$ .
Threshold potential? $\approx -55\,\text{mV}$ .
Stoichiometry of the Na⁺/K⁺ pump? $3\,\text{Na}^+{\text{out}}$ : $2\,\text{K}^+{\text{in}}$ .
Continuous vs Saltatory? Unmyelinated vs Myelinated.
3 ways to clear NT? Diffusion, enzymatic breakdown, re-uptake.
EPSP vs IPSP ion examples? $\text{Na}^+$ in vs $\text{Cl}^-$ in.

Big Picture Connections & Real-World Relevance

Electrical signaling underlies every conscious thought, motor action, and sensory experience—malfunctions manifest as neurological or psychiatric disease.
Pharmacology (local anesthetics, antidepressants, antiepileptics) exploits ion channels and synaptic machinery to modulate neural communication.
Ethical dimension: Access to treatments (e.g., MS disease-modifying drugs), cognitive enhancement debates (nootropics) hinge on our grasp of synaptic physiology.