Transport Across Cell Membranes – Comprehensive Bullet-Point Notes

Movement of Materials Across Cell Membranes (General Transport Overview)

• Cells must control the exchange of molecules, ions, particles, and entire vesicles with their surroundings.
  • Transport occurs either in bulk (vesicle-mediated) or through specific membrane proteins.
• Two broad protein classes mediate trans-membrane traffic:
  • Transporters / Carriers / Pumps – undergo conformational change for each substrate.
  • Channels – form hydrophilic pores; do NOT change shape for every ion that passes.
• Transport direction & energy use:
  • Passive transport: down electrochemical or concentration gradient; no external energy.
  • Active transport: against gradient; always energy-requiring (ATP, ion gradient, light, or mechanical force).
• Key concepts to master:
  • Membrane potential, electrochemical gradients, bulk transport routes, channel gating, and the neuron as an archetypal excitable cell.

Bulk Transport (Vesicle-Mediated)

• Required when cargo is too large for single transport proteins.
• Often active (ATP/GTP hydrolysis, cytoskeletal motors, etc.).

Endocytosis (Import)

• Phagocytosis – “cell eating”
  • Membrane extends pseudopodia around large particle → phagosome/vacuole.
  • Common in macrophages, protozoa.
• Pinocytosis – “cell drinking”
  • Membrane invaginates, encloses extracellular fluid → small pinocytic vesicle.
  • Constitutive, non-specific uptake of solutes.
• Receptor-mediated endocytosis (RME)
  • Highly specific; ligand binds surface receptor → clathrin coat assembles → coated pit → coated vesicle internalized.
  • Allows concentration of scarce nutrients (e.g., LDL, transferrin).

Exocytosis (Export)

• Intracellular vesicle (often from Golgi) docks & fuses with plasma membrane → releases contents outside.
  • Important for secretion of neurotransmitters, hormones, membrane protein delivery, and waste removal.

Membrane Permeability & Barriers

• Pure lipid bilayers are impermeable to:
  • Charged atoms (ions) and most uncharged polar molecules beyond ~3–4 carbons.
• Diffusion rate across protein-free bilayer increases with:
  • Smaller size,
  • Greater hydrophobicity (non-polarity).
• Water can diffuse slowly, but specialized aquaporins accelerate its movement.

Passive Transport: Facilitated Diffusion

• Utilizes membrane proteins but no external energy.
• Moves solutes down their electrochemical gradient.

Channel Proteins

• Lined with hydrophilic amino acids forming aqueous pore.
  • Can be continuously open or gated (voltage, ligand, mechanical, etc.).
• Examples:
  • Aquaporins → rapid \mathrm{H_2O} transport.
  • Ion channels in muscle → initiate contraction.

Carrier / Transport Proteins (Facilitated Carriers)

• Bind specific solute → conformational change → release on opposite side.
• Reversible; direction depends on gradient.
• Example: GLUT family for glucose.

Active Transport

• Moves solute up its concentration or electrochemical gradient.
• Energy sources:
  • ATP hydrolysis (P-type, V-type, ABC transporters).
  • Coupled transport – uses energy stored in gradient of second solute (symport or antiport).
  • Light or mechanical force (e.g., bacteriorhodopsin, stereocilia tip links).
• Terminology:
  • Pump ≈ active transporter.

Illustrative Active Transporters

• Na+ / K+ ATPase (Na+ pump)
  • Expels 3 \mathrm{Na^+}, imports 2 \mathrm{K^+} per ATP → major contributor to resting membrane potential & Na+ gradient.
• Ca\^{2+} ATPase (PM & SR/ER)
  • Maintains cytosolic [\mathrm{Ca^{2+}}] at \sim 10^{-4} mM; critical for signaling & muscle relaxation.
• H+ pumps
  • V-type (lysosomes, vacuoles) & P-type (plants/fungi PM) → acidify compartments, drive secondary transport.
• Gradient-driven (secondary) pumps
  • Na+-glucose symport in gut epithelium → imports glucose against gradient by coupling to Na+ down gradient.
  • Na+/H+ exchanger → pH regulation.

Osmosis & Aquaporins

• Osmosis: net water diffusion down its own concentration gradient.
  • Water moves toward region of higher solute concentration.
• Aquaporin channels drastically increase water permeability, vital in kidney, plant vacuoles, erythrocytes.

Ion Concentrations & Membrane Potential

• Intracellular vs. Extracellular ion distribution (typical mammalian cell):
  • High \mathrm{K^+} inside (~140 mM), high \mathrm{Na^+} outside (~145 mM), high \mathrm{Cl^-} outside (~110 mM).
• Membrane potential (V_m) arises from charge separation.
  • Dominated by K+ leak channels and trapped intracellular anions.

Electrochemical Gradient Components

• Chemical (concentration) term
• Electrical term (membrane potential)
• Combined force dictates passive ion movement direction.

Nernst Equation (37 °C, z = +1)

• V = 62 \log{10}\left(\dfrac{Co}{C_i}\right)\ \text{mV}
  • Equilibrium reached when electrical & chemical forces balance.

Ion Channels: Selectivity & Gating

• Selectivity filter discriminates ions by size & hydration shell (e.g., K+ channel excludes Na+).
• Channels spontaneously flicker between open & closed states (“gating noise”).
• Types of gating stimuli:
  • Voltage-gated (respond to V_m changes)
  • Ligand-gated (extracellular or intracellular ligands)
  • Mechanically-gated (stretch, pressure, sound)

Specialized Examples

• Hair cell stereocilia: tip-link tension opens mechano-gated cation channels → auditory transduction.
• Mimosa pudica: mechanosensitive & voltage-gated channels collaborate to close leaves upon touch.

Neuron Case Study

• Action potential (AP) = regenerative, all-or-none depolarization that travels along axon.
  • Triggered when depolarization reaches threshold (~-55 mV) opening voltage-gated Na+ channels.

Phases of AP

1. Resting: K+ leak sets V_m (~-70 mV).
2. Depolarization: Na+ channels open → influx.
3. Peak/Inactivation: Na+ channels inactivate; voltage-gated K+ channels open.
4. Repolarization & Hyperpolarization: K+ efflux; channels close.
5. Restoration: Na+/K+ ATPase re-establishes gradients.

Propagation

• Local depolarization opens adjacent Na+ channels → AP moves unidirectionally (refractory period behind).

Synaptic Transmission

• Arrival of AP at nerve terminal opens voltage-gated Ca\^{2+} channels.
  • \mathrm{Ca^{2+}} influx triggers synaptic vesicle fusion (exocytosis) → neurotransmitter released.
• Postsynaptic membrane: transmitter-gated channels convert chemical signal back to electrical.
  • Excitatory (e.g., acetylcholine, glutamate) → cation influx (Na+, Ca\^{2+}) depolarizes.
  • Inhibitory (e.g., GABA, glycine) → Cl\^- influx or K+ efflux hyperpolarizes.

Representative Ion Channels & Functions (Table Highlights)

• K+ leak – resting potential maintenance.
• Voltage-gated Na+ – AP initiation.
• Voltage-gated K+ – AP termination.
• Voltage-gated Ca\^{2+} – neurotransmitter release.
• Acetylcholine receptor (nicotinic) – excitatory NMJ signaling.
• Glutamate receptors – major excitatory synapses in CNS.
• GABA / Glycine receptors – inhibitory Cl\^- channels.
• Mechanically-gated cation channels – hearing & touch.

Integrated Physiology / Real-world Relevance

• Na+/K+ pump consumes ~30 % of resting ATP in neurons; drug target (cardiac glycosides).
• Defects in RME (e.g., faulty LDL receptor) → familial hypercholesterolemia.
• Aquaporin mutations → nephrogenic diabetes insipidus.
• Voltage-gated Na+ channel toxins (tetrodotoxin) block APs → paralysis.
• Synaptic channel modulators form basis of many anesthetics, anticonvulsants, insecticides.

Ethical & Philosophical Notes

• Understanding neuronal ion channels underpins treatments for neurodegenerative disorders, but also raises questions about consciousness manipulation.
• Gene editing to correct channelopathies necessitates careful societal oversight.

Numerical / Statistical & Tabular Data (Select)

• Typical intracellular [\mathrm{Na^+}] = 5–15 mM; extracellular = 145 mM.
• Cytosolic free [\mathrm{Ca^{2+}}] ≈ 10^{-4}\ \text{mM} vs. 1–2 mM outside (10,000-fold gradient).
• Na+/K+ pump exchanges 3 Na+ : 2 K+ per ATP.
• Nernst slope at 37 °C = 62 mV per 10-fold concentration change for monovalent cations.

Key Equations & Formulas (LaTeX-formatted)

• Nernst (z = +1): V = 62 \log{10}\left(\dfrac{Co}{C_i}\right)
• Electrochemical potential (qualitative): \Delta\mu = RT \ln\left(\dfrac{Co}{Ci}\right) + zF\Delta\psi
  • R (gas constant), T (temperature), F (Faraday constant), \Delta\psi (membrane potential).

Connections to Prior Content & Foundations

• Builds on fluid-mosaic model (Chapter 5) ⇒ dynamic lipid/protein environment.
• Relates to Chapter 4 cytoskeleton: actin/myosin drive phagocytosis; microtubule motors guide vesicles for exocytosis.
• Prepares for bioenergetics chapters: proton gradients across inner mitochondrial membrane drive ATP production (chemiosmotic principle shared with H+-driven transport here).

Study Checklist

• Define & contrast phagocytosis, pinocytosis, RME, exocytosis.
• Explain how electrochemical gradient differs from simple concentration gradient.
• Trace path of glucose from gut lumen → blood using Na+-glucose symport + GLUT.
• Derive equilibrium potential for K+ given intra/extracellular concentrations using Nernst.
• Illustrate sequence of events in neuronal AP and synaptic transmission.
• Memorize key pump/channel examples and their inhibitors.