Nervous System – Impulse Propagation

Neuronal Anatomy and Electrical Excitability

• A typical motor neuron possesses dendrites, a cell body (soma), an axon hillock, initial segment, axon, axon collaterals, and axon terminals capped by synaptic end-bulbs.
• Cytoplasmic specializations
– Nissl bodies (rough ER) for protein synthesis.
– Neurofibrils for cytoskeletal integrity.
– Abundant mitochondria to meet high ATP demand.
• Schwann-cell wrapping forms the myelin sheath; its outer nucleated layer is the neurolemma. Gaps between successive Schwann cells constitute the Nodes of Ranvier—critical for saltatory conduction.
• Major functional property: electrical excitability—the capacity to generate and propagate electrical signals via opening/closing of ion channels for Na⁺, K⁺, Ca²⁺.

Membrane Potentials and the Ionic Basis

• Resting membrane potential (RMP) ≈ $-70\,\text{mV}$.
– Arises because K⁺ diffuses outward leaving an excess of negative charge on the inner leaflet of the plasma membrane.
– Only a thin shell of charges adjacent to the membrane is involved; the bulk cytosol remains electrically neutral.
• Ionic asymmetry
– Extracellular fluid (ECF): more $\text{Na}^+$ and $\text{Cl}^-$.
– Cytosol: more $\text{K}^+$, organic phosphates (PO₄³⁻), and negatively charged amino acids.
– Membrane permeability is greater for K⁺ than for Na⁺ at rest, intensifying negative potential.
• K⁺ equilibrium (Nernst) potential ≈ $-90\,\text{mV}$; because Na⁺ can leak inward, actual RMP is less negative (≈ $-70\,\text{mV}$).
• Na⁺/K⁺ ATPase maintains gradients: $3\,\text{Na}^+$ pumped out for every $2\,\text{K}^+$ pumped in, consuming ATP.

Ion Channels

• Leak channels – always open; more numerous for K⁺ → chief determinant of RMP.
• Gated channels – open/close in response to stimuli.

1. Voltage-gated
   • Sense membrane potential changes.
   • Essential for action‐potential (AP) generation & conduction.
2. Chemically (ligand)-gated
   • Respond to neurotransmitters, hormones, or specific ions.
   • Example: nicotinic ACh receptor on motor end-plate.
3. Mechanically-gated
   • Open by membrane deformation (touch, stretch, vibration).
   • Channel states for voltage-gated Na⁺: (i) closed but capable of opening, (ii) open, (iii) closed & inactivated (cannot reopen until reset).

Graded Potentials (GPs)

• Localized, decremental changes in membrane voltage arising mainly on dendrites & soma after chemically or mechanically-gated channels open.
• Depolarizing GP – membrane becomes less negative.
• Hyperpolarizing GP – membrane becomes more negative.
• Amplitude is proportional to stimulus strength (number & duration of channels opened).
• Travel only a short distance; if sufficient depolarization reaches axon hillock (initial segment), an AP is triggered.

Action Potentials (APs)

• Rapid, self-propagating, all-or-none impulses carried by the axonal membrane; last ≈ $1\,\text{ms}$.
• Require two voltage-gated channels:
– Na⁺ channels → rapid depolarization.
– K⁺ channels → repolarization & possible hyperpolarization.

Phases

1. Resting state: $V_m = -70\,\text{mV}$; channels closed.
2. Depolarization to threshold: graded potentials bring $V_m$ to $-55\,\text{mV}$ (threshold).
3. Na⁺ channel activation: Na⁺ rushes in → membrane potential shoots to ≈ $+30\,\text{mV}$.
4. Na⁺ inactivation & K⁺ activation: Na⁺ channels inactivate; slower K⁺ channels now open → K⁺ efflux.
5. Repolarization: membrane returns toward RMP.
6. After-hyperpolarization: K⁺ channels may stay open long enough to overshoot (≈ $-90\,\text{mV}$) before closing.

Refractory Periods

• Absolute refractory period: second AP impossible—Na⁺ channels are inactivated.
• Relative refractory period: Na⁺ channels reset but K⁺ still open; suprathreshold stimulus can elicit AP.

Propagation Along Axons

1. Continuous conduction
   • Unmyelinated fibers; each adjacent patch depolarizes next—slow.
2. Saltatory conduction
   • Myelinated fibers; AP “jumps” node-to-node.
   • Current flows only at Nodes of Ranvier where channels cluster, giving far greater velocity and energy efficiency.

Fiber Types and Conduction Velocity

• Velocity increases with axon diameter & myelination; cooling slows it.
• A fibers: large, myelinated, $12–130\,\text{m·s}^{-1}$; somatic sensory (touch, proprioception), motor to skeletal muscle; brief absolute refractory.
• B fibers: smaller, myelinated; visceral afferents & preganglionic autonomic efferents; longer refractory.
• C fibers: smallest, unmyelinated, $\approx0.5\,\text{m·s}^{-1}$; some pain, temperature, postganglionic autonomic.

Synaptic Transmission Overview

• Synapse: junction where a presynaptic neuron communicates with a postsynaptic target (neuron, muscle, or gland).
• Structural arrangements: axodendritic, axosomatic, axoaxonic.

Electrical Synapses

• Direct ionic current via gap junctions composed of connexons.
• Occur in visceral smooth & cardiac muscle, some CNS circuits.
• Advantages: near-instantaneous transmission, synchronization of cell groups, bidirectional flow.

Chemical Synapses

• Pre- & postsynaptic membranes separated by a synaptic cleft; transmission is one-way and slower (synaptic delay ≈ 0.5 ms).
• Neurotransmitter produces a graded postsynaptic potential.

Cholinergic Synapse Example (ACh)

STEP 1 An AP depolarizes the synaptic knob.
STEP 2 Voltage-gated $\text{Ca}^{2+}$ channels open; $\text{Ca}^{2+}$ influx triggers exocytosis of ACh vesicles.
STEP 3 ACh diffuses across cleft, binds ligand-gated Na⁺ channels → depolarizing EPSP; if threshold reached, postsynaptic AP starts.
STEP 4 Acetylcholinesterase (AChE) hydrolyzes ACh to terminate signal.

Neurotransmitters Beyond ACh

• Norepinephrine (NE) – adrenergic synapses; excitatory in brain & ANS.
• Dopamine – excitatory or inhibitory; essential for motor control (deficit → Parkinson’s tremor; excess in certain pathways → psychosis).
• Serotonin – modulates attention, mood; low levels linked to depression.
• Gamma-aminobutyric acid (GABA) – principal inhibitory transmitter in brain; opens Cl⁻ channels, dampens neuronal firing, reduces anxiety.
– GABA potentiated by barbiturates & benzodiazepines.
– Antiepileptics (e.g., phenytoin, valproic acid) slow Na⁺ influx, complementing inhibition.

Postsynaptic Potentials

• Excitatory postsynaptic potential (EPSP) – depolarizing graded potential via cation entry.
• Inhibitory postsynaptic potential (IPSP) – hyperpolarizing graded potential; commonly involves Cl⁻ influx (GABA-gated) or K⁺ efflux.
• Neuronal output depends on algebraic summation of EPSPs & IPSPs at the axon hillock.

Spatial and Temporal Summation

• Spatial summation: simultaneous input from multiple presynaptic terminals at different spots.
• Temporal summation: rapid, successive firing of a single terminal.
• Both raise probability of reaching threshold at the trigger zone.

Neurotransmitter Removal Mechanisms

1. Diffusion away from synaptic cleft.
2. Enzymatic degradation (e.g., AChE for acetylcholine).
3. Reuptake by presynaptic neuron or surrounding glia (e.g., NE transporter).