The role of volume-sensitive ion transport systems in regulation of epithelial transport

• Published in: Comparative biochemistry and physiology. Part A, Molecular & integrative physiology Vol. 148; no. 1; pp. 29 - 43
• Main Authors: Hoffmann, E.K., Schettino, T., Marshall, W.S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2007
• Subjects: Anguilla anguilla; Animals; Eels - physiology; Epithelium - metabolism; Fundulus heteroclitus; Intestine; Ion Transport; Na +, K +, 2Cl − cotransport; NKCC; Opercular epithelium; Protein kinase; RVD; RVI; SPAK; Ussing chamber; RVD; PTPs; RVI; Anguilla anguilla; Ste20; LTD 4; JNK; PGE 2; BK; CK2; Na +, K +, 2Cl − cotransport; FW; WNK; Intestine; SK; SPAK; IK; MLCK; SW; BAE; OSR1; PKA; PTKs; PKC; Ussing chamber; EATC; MAPK; Fundulus heteroclitus; 2P-4TM; Opercular epithelium; EET; Protein kinase; VRAC; NKCC; TASK-2; ELA
• ISSN: 1095-6433; 1531-4332
• DOI: 10.1016/j.cbpa.2006.11.023

This review focuses on using the knowledge on volume-sensitive transport systems in Ehrlich ascites tumour cells and NIH-3T3 cells to elucidate osmotic regulation of salt transport in epithelia. Using the intestine of the European eel ( Anguilla anguilla) (an absorptive epithelium of the type described in the renal cortex thick ascending limb (cTAL)) we have focused on the role of swelling-activated K +- and anion-conductive pathways in response to hypotonicity, and on the role of the apical (luminal) Na +–K +–2Cl − cotransporter (NKCC2) in the response to hypertonicity. The shrinkage-induced activation of NKCC2 involves an interaction between the cytoskeleton and protein phosphorylation events via PKC and myosin light chain kinase (MLCK). Killifish ( Fundulus heteroclitus) opercular epithelium is a Cl −-secreting epithelium of the type described in exocrine glands, having a CFTR channel on the apical side and the Na +/K +ATPase, NKCC1 and a K + channel on the basolateral side. Osmotic control of Cl − secretion across the operculum epithelium includes: (i) hyperosmotic shrinkage activation of NKCC1 via PKC, MLCK, p38, OSR1 and SPAK; (ii) deactivation of NKCC by hypotonic cell swelling and a protein phosphatase, and (iii) a protein tyrosine kinase acting on the focal adhesion kinase (FAK) to set levels of NKCC activity.