Cell Membrane Transport | Dr. Najeeb Lectures

What the Lecture Covers

1. Passive Transport (no ATP required)

• Simple Diffusion - solutes move down their concentration gradient (high → low). Covered at 02:24.
• Facilitated Diffusion - passive movement aided by membrane channel or carrier proteins (e.g., glucose channels, sodium channels, ligand-gated channels). Covered at 16:17 onward.
  • Voltage-gated sodium channels (19:55)
  • Ligand-operated/gated channels (27:08)
  • Transporter/carrier proteins (32:27)

2. Active Transport (ATP required)

• Primary Active Transport - uses ATP directly. Examples: Na⁺/K⁺ ATPase pump, Ca²⁺ transporters (39:16 onward).
• Secondary Active Transport - exploits electrochemical gradients established by primary pumps. Examples: sodium-glucose co-transporter (SGLT), counter-transport. Covered at 42:46.

3. Vesicular Transport (Bulk Transport)

• Endocytosis (bringing material IN):
  • Pinocytosis - cell "drinking" (1:14:55)
  • Phagocytosis - cell "eating," e.g., macrophages (1:16:40)
  • Receptor-mediated endocytosis - e.g., LDL uptake in liver cells (1:17:53)
• Exocytosis - expelling material OUT of the cell (1:23:25)

Key Concepts at a Glance

Teaching Style

Cell Membrane Transport - Exam Notes

Based on Dr. Najeeb Lectures | Sources: Guyton & Hall, Ross Histology, Goodman & Gilman

1. THE CELL MEMBRANE - Overview

• The plasma membrane is a phospholipid bilayer that acts as a selective barrier between the intracellular and extracellular environments.
• It regulates homeostasis: allows nutrients in, keeps wastes out, and blocks harmful substances.
• Key rule: The lipid bilayer is a natural barrier to most polar/charged molecules - they need help to get through.

2. OVERVIEW OF TRANSPORT TYPES

3. PASSIVE TRANSPORT (No ATP)

3a. Simple Diffusion

Histology: A Text and Atlas (Ross), p.143

• Movement of molecules down their concentration gradient (high → low) with no energy and no protein needed.
• Driven purely by random kinetic motion (Brownian motion).

• Small, lipid-soluble molecules: O₂, CO₂, N₂, alcohols, steroid hormones, fat-soluble vitamins (A, D, E, K)
• O₂ and CO₂ are the classic examples - they dissolve directly in the lipid bilayer.

• Concentration difference across membrane: Net diffusion ∝ (C_outside - C_inside)
• Lipid solubility of the substance
• Size and number of membrane pores
• Temperature

3b. Facilitated Diffusion

i. Channel Proteins (Ion Channels)

• Form hydrophilic pores/tunnels through the membrane.
• Contain a pore domain (ion-selectivity filter) - regulates which ions pass.
• Transport is fast (ions flow freely when open).

• Aquaporins - special channel proteins for water. At least 13 types in mammals. Aquaporin-2 density is regulated by ADH (antidiuretic hormone). Water diffuses through them in single file, so fast that the red blood cell membrane transports 100x its own volume per second. (Guyton & Hall, p.65)

ii. Carrier Proteins

• Bind a specific molecule, then undergo conformational change to shuttle it across.
• Highly selective - usually one type of molecule per carrier.
• Show a maximum transport rate (Vmax) - at high concentrations, carriers become saturated and rate plateaus. This is the key difference from simple diffusion.
• Examples: GLUT transporters (glucose into cells), amino acid carriers.

• GLUT transporters are carrier proteins - not Na⁺-dependent - facilitate diffusion of glucose into most cells.
• In the gut and kidney, glucose is absorbed via SGLT (active transport - see below).

• Simple diffusion: rate keeps increasing linearly with concentration.
• Facilitated diffusion: rate plateaus at Vmax (carrier saturation).

4. ACTIVE TRANSPORT (Requires Energy)

4a. Primary Active Transport

• Uses ATP directly to drive the pump.
• Most important example: Na⁺/K⁺ ATPase pump (sodium-potassium pump).

Na⁺/K⁺ ATPase - The Master Pump

• Location: Basolateral membrane of most cells.
• Action: Pumps 3 Na⁺ OUT and 2 K⁺ IN per cycle, using 1 ATP.
• Net result: Creates low intracellular Na⁺ (12 mEq/L inside vs. 140 mEq/L outside) and a negative intracellular charge (-70 mV).
• This creates the electrochemical gradient exploited by secondary active transport.

• Ca²⁺-ATPase (SERCA pump): pumps Ca²⁺ into the ER or out of the cell. Keeps cytoplasmic Ca²⁺ very low (~10⁻⁷ mol/L).
• H⁺/K⁺ ATPase: in stomach parietal cells - secretes gastric acid. Blocked by PPIs (omeprazole, pantoprazole).

4b. Secondary Active Transport

• Does not use ATP directly.
• Uses the electrochemical gradient of Na⁺ (created by the Na⁺/K⁺ pump) to drive a second substance against its gradient.
• So it indirectly depends on ATP (because the pump that made the gradient used ATP).

SGLT (Sodium-Glucose Co-Transporter) - High Yield!

• SGLT1 - in small intestine (absorbs glucose from gut lumen) and kidney proximal tubule (late segment).
• SGLT2 - in kidney proximal tubule (early segment; reabsorbs ~90% of filtered glucose).
• Mechanism: Na⁺ flows down its gradient INTO the cell, dragging glucose against its gradient into the cell simultaneously.
• Clinical relevance: SGLT2 inhibitors (gliflozins - dapagliflozin, empagliflozin) block this transporter → glucosuria → lower blood glucose in Type 2 DM. Also have cardioprotective and renoprotective effects.

5. VESICULAR TRANSPORT (Bulk Transport)

Histology: A Text and Atlas (Ross), p.144

5a. Endocytosis (INTO the cell)

Three Major Types:

• Micropinocytosis - nonspecific ingestion of extracellular fluid and small proteins via vesicles < 150 nm.
  • Constitutive process (happens continuously).
  • Uses caveolin and flotillin proteins in lipid rafts.
  • Clathrin-independent and actin-independent.
  • Especially prominent in: endothelial cells of blood vessels, smooth muscle cells.
• Macropinocytosis - non-specific uptake of large volumes of extracellular fluid.
  • Actin-dependent - actin cytoskeleton rearranges to form membrane ruffles.
  • Vesicles (macropinosomes) are large - enter cytoplasm and fuse with lysosomes.

• Ingestion of large particles - bacteria, dead cells, debris.
• Performed by specialized cells: macrophages, neutrophils, dendritic cells.
• Requires actin cytoskeleton remodeling.
• Particles are engulfed into a phagosome, which fuses with a lysosome → phagolysosome → enzymatic degradation.
• This is an immune defense mechanism.

• Most specific form of endocytosis.
• Cell surface receptors bind specific ligands (e.g., LDL, transferrin, insulin, hormones).
• The receptor-ligand complex clusters at clathrin-coated pits on the plasma membrane.
• The pit invaginates and pinches off as a clathrin-coated vesicle.
• Inside the cell: vesicle loses its clathrin coat → fuses with early endosome.
• The ligand is degraded in lysosomes; the receptor is often recycled back to the surface.
• Classic example: LDL receptor uptake in liver cells (LDL carries cholesterol). Mutation in LDL receptor → familial hypercholesterolemia.

5b. Exocytosis (OUT of the cell)

• Secretory vesicles (from Golgi apparatus) move to the plasma membrane and fuse with it, releasing cargo into the extracellular space.
• Examples: neurotransmitter release from synaptic vesicles, hormone secretion, mucus release.
• After exocytosis, vesicular membrane is retrieved by endocytosis (prevents cell from swelling).

6. QUICK SUMMARY TABLE - High Yield for Exams

7. HIGH-YIELD EXAM POINTS

1. Simple vs. Facilitated diffusion: Simple = linear rate increase; Facilitated = Vmax saturation.
2. Na⁺/K⁺ ATPase: Pumps 3 Na⁺ OUT, 2 K⁺ IN per ATP. Creates -70 mV inside cell.
3. SGLT2 inhibitors (e.g., dapagliflozin, empagliflozin) - used in T2DM. Cause glucosuria.
4. Aquaporins - channel proteins for water only. At least 13 types. AQP2 regulated by ADH.
5. Clathrin - coats endocytic vesicles in receptor-mediated endocytosis.
6. Caveolin/Flotillin - proteins in micropinocytosis (clathrin-independent).
7. Exo- and endo-cytosis are coupled: tetanus/botulinum toxin blocks both via SNARE proteins.
8. Lipid-soluble substances cross freely through the bilayer (no help needed).
9. Carrier proteins show Vmax (saturation kinetics); channels do not.
10. Secondary active transport does not use ATP directly - it uses the Na⁺ gradient built by the Na⁺/K⁺ pump.