Membrane Transport: Channels, Carriers, and Pumps
Concept Name
Membrane Transport
Genetic Loci
SLC12A1 (15q21.1) encodes NKCC2 – mutations cause Bartter syndrome type I. CFTR (7q31.2) encodes the cystic fibrosis transmembrane conductance regulator (a Cl⁻ channel).
Intracellular Cascade
Na⁺/K⁺‑ATPase creates electrochemical gradients; secondary active transport (SGLT1, NKCC) couples solute movement to Na⁺ gradient. Ion channels (voltage‑gated, ligand‑gated) facilitate passive diffusion. Aquaporins allow water transport.
Required Cofactors
Mg²⁺ is required for ATPase activity. Ca²⁺ is essential for neurotransmitter release via voltage‑gated Ca²⁺ channels.
Histology Stains
Immunohistochemistry for Na⁺/K⁺‑ATPase shows basolateral localization in renal tubules. Aquaporin‑2 stains apical membrane of collecting duct principal cells.
EM Findings
Freeze‑fracture EM reveals intramembrane particles representing ion channels and pumps. Tight junctions appear as anastomosing strands sealing the paracellular space.
Knockout Phenotype
Knockout of NKCC2 (Slc12a1) in mice causes severe polyuria, salt wasting, and death within 2 weeks unless treated with indomethacin. CFTR knockout mice have intestinal obstruction and pancreatic insufficiency.
Specific Toxins
Ouabain inhibits Na⁺/K⁺‑ATPase. Amiloride blocks ENaC (epithelial Na⁺ channel). Furosemide inhibits NKCC2 in the thick ascending limb of Henle.