I. Nervous System

Cells of the Nervous System

The nervous system is composed of specialized cells that facilitate rapid communication and integration of body functions.

• Neurons: Responsible for signal transmission via electrical impulses.

• Glia: Supportive cells with various functions:

  • Microglia: Immune cells, phagocytosis of debris.

  • Oligodendrocytes (CNS) & Schwann cells (PNS): Myelin production for insulation.

  • Astrocytes: Provide support, maintain blood-brain barrier (BBB), regulate neurotransmitters.

Neuron Anatomy

Neurons have specialized structures for receiving, integrating, and transmitting signals.

• Soma: Integrates incoming signals.

• Dendrites: Receive input from other neurons.

• Axon: Conducts action potentials (AP) away from the soma.

• Myelin/Nodes of Ranvier: Enable saltatory conduction, increasing speed of AP propagation.

• Synaptic boutons/synapses: Sites of chemical/electrical signaling to other cells.

Resting Membrane Potential

The resting membrane potential (RMP) is the electrical potential difference across the neuronal membrane at rest.

• Maintained by Na+/K+ pump and K+ leak channels.

• Calculated using the Goldman equation:

Action Potential

Action potentials are rapid changes in membrane potential that propagate along axons.

1. Depolarization: Na+ channels open, Na+ influx.

2. Repolarization: K+ channels open, K+ efflux.

3. Hyperpolarization: Continued K+ efflux.

• AP initiated at axon hillock, travels along axon.

• Myelinated: Fast, saltatory conduction; unmyelinated: Slow, continuous conduction.

Synapses

Synapses are specialized junctions for communication between neurons.

• Electrical synapses: Fast, via gap junctions.

• Chemical synapses: Neurotransmitter release, Ca2+ influx, postsynaptic receptor binding.

• Excitatory: Acetylcholine; Inhibitory: GABA, glycine.

• Neurotransmitters can modulate ion channels, vesicle release, or receptor activity.

II. Cell Signaling

Key Terms

• Receptor: Detects extracellular signals.

• Ligand: Signaling molecule that binds to a receptor.

• Effector: Produces a cellular response.

Signaling Types

Cells communicate using various signaling mechanisms:

• Contact-dependent: Membrane-bound ligands.

• Paracrine: Local, short-distance signaling.

• Synaptic: Neuronal, neurotransmitter release.

• Endocrine: Long-distance, hormones via bloodstream.

• Fast: Ion channels; Slow: Gene expression changes.

Receptors

• Ligand-gated ion channels: Rapid response to neurotransmitters.

• GPCRs (G-protein coupled receptors): 7 transmembrane helices, activate G-proteins, cAMP/IP3/DAG pathways.

• RTKs (Receptor tyrosine kinases): Dimerize, autophosphorylation, activate Ras/MAPK pathway.

• Ser/Thr kinases: Phosphorylate serine/threonine residues.

• Non-receptor TKs (JAK-STAT): Phosphorylate STAT, regulate gene transcription.

• Nuclear receptors: Ligand-activated, regulate gene transcription in nucleus.

Second Messengers

• cAMP: Activates protein kinase A (PKA).

• IP3/DAG: IP3 triggers Ca2+ release, DAG activates protein kinase C (PKC).

• Ca2+: Activates calmodulin, CAMK, phosphorylation cascades.

Feedback Loops

• Negative feedback: Dampens signal, maintains homeostasis.

• Positive feedback: Amplifies signal, can drive rapid responses.

High-Yield Integration

• Neurons & signaling: AP → Ca2+ influx → neurotransmitter release → receptor activation → postsynaptic response.

• Motor proteins & cytoskeleton: Intracellular transport, movement, cytoskeletal guidance.

III. Cytoskeletal Systems

I. Cytoskeleton Overview

The cytoskeleton is a dynamic network of protein filaments providing structural support, intracellular transport, motility, and cell division.

• Three main filament types:

  Filament	Size (nm)	Polarity	Main Function
  Microfilaments (Actin)	7-8	Yes (+/-)	Cell shape, motility, endocytosis, microvilli, muscle contraction
  Intermediate Filaments	8-12	No	Mechanical strength, structural support, nuclear envelope anchoring
  Microtubules	25	Yes (+ at MTOC; - at periphery)	Tracks for transport, mitotic spindle, organelle positioning, cilia/flagella structure

II. Microtubules

Microtubules are hollow tubes composed of α/β-tubulin dimers, essential for cell division, transport, and motility.

• Composition: α/β-tubulin dimers (bind GTP).

• Polarity: Dynamic (+ end grows, - end anchored at MTOC/centrosome).

• Dynamics: GTP cap stabilizes plus end; dynamic instability (growth ↔ catastrophe ↔ rescue).

• Microtubule-Associated Proteins (MAPs): Stabilize, regulate, and organize microtubules (Tau, MAP2, etc.).

• Drugs: Taxol (stabilizes), Colchicine/Nocodazole (depolymerizes).

• Special Structures: Basal bodies (cilia/flagella).

III. Microfilaments (Actin)

Microfilaments are thin, flexible filaments composed of actin, involved in cell shape, movement, and muscle contraction.

• Composition: G-actin monomers polymerize to form F-actin filaments.

• Polarity: + end grows faster than - end.

• Functions: Cell shape, motility (lamellipodia/filopodia), endocytosis, microvilli, cytokinesis.

• Regulation:

  • Polymerization: Profilin, Cofilin, CapZ.

  • Crosslinking/Bundling: Filamin, Villin, Fimbrin, Gelatin.

  • Branched actin: Arp2/3, WASP.

  • Drugs: Phalloidin (stabilizes), Cytochalasin (inhibits polymerization).

IV. Intermediate Filaments

Intermediate filaments provide mechanical strength and maintain cell integrity.

• Composition: Cell-specific fibrous proteins (keratin, lamins, vimentin, neurofilaments).

• Polarity: None (stable, rope-like).

• Functions: Mechanical strength, nuclear/cytoplasmic anchoring, tissue integrity.

V. Motor Proteins

Motor proteins convert chemical energy into mechanical work, moving cargo along cytoskeletal filaments.

VI. Cellular Motility

Cellular motility is driven by cytoskeletal elements and motor proteins.

• Microtubule-based: Organelle transport, mitotic spindle, cilia/flagella beating.

• Actin-based:

  • Non-muscle: Lamellipodia/filopodia, cell crawling.

  • Muscle: Sarcomeres—sliding filament mechanism (actin + myosin).

  • Myosin-binding to actin: Exposed when Ca2+ binds troponin → ATP powers contraction.

VII. Cilia & Flagella

Cilia and flagella are microtubule-based structures responsible for cell movement and fluid transport.

• Axoneme: 9+2 microtubule arrangement.

• Movement: Dynein causes microtubule sliding → bending.

• Basal body: Anchors axoneme.

High-Yield Notes

• Microtubules: Highway for organelle & vesicle trafficking; + end = periphery, - end = MTOC.

• Cellular defects: Mutations in motor proteins disrupt motility.

• Dynamics: Actin is stable at M.T. ends; dynamic at +/– ends.

• Drugs: Can stabilize or destabilize filaments, affecting cell division and motility.