Clcn2 encodes the hyperpolarization-activated chloride channel in the ducts of mouse salivary glands

Romanenko, VG; Nakamoto, T.; Catalan, MA; Gonzalez-Begne, M; Schwartz, GJ; Jaramillo, Y.; Sepulveda, FV; Figueroa, CD; Melvin, JE

Abstract

Transepithelial Cl- transport in salivary gland ducts is a major component of the ion reabsorption process, the final stage of saliva production. It was previously demonstrated that a Cl- current with the biophysical properties of ClC-2 channels dominates the Cl- conductance of unstimulated granular duct cells in the mouse submandibular gland. This inward-rectifying Cl- current is activated by hyperpolarization and elevated intracellular Cl- concentration. Here we show that ClC-2 immunolocalized to the basolateral region of acinar and duct cells in mouse salivary glands, whereas its expression was most robust in granular and striated duct cells. Consistent with this observation, nearly 10-fold larger ClC-2-like currents were observed in granular duct cells than the acinar cells obtained from submandibular glands. The loss of inward-rectifying Cl- current in cells from Clcn2-/- mice confirmed the molecular identity of the channel responsible for these currents as ClC-2. Nevertheless, both in vivo and ex vivo fluid secretion assays failed to identify significant changes in the ion composition, osmolality, or salivary flow rate of Clcn2-/- mice. Additionally, neither a compensatory increase in Cftr Cl- channel protein expression nor in Cftr-like Cl- currents were detected in Clcn2 null mice, nor did it appear that ClC-2 was important for blood-organ barrier function. We conclude that ClC-2 is the inward-rectifying Cl- channel in duct cells, but its expression is not apparently required for the ion reabsorption or the barrier function of salivary ductal epithelium. Copyright © 2008 the American Physiological Society.

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Título según WOS: Clcn2 encodes the hyperpolarization-activated chloride channel in the ducts of mouse salivary glands
Título según SCOPUS: Clcn2 encodes the hyperpolarization-activated chloride channel in the ducts of mouse salivary glands
Título de la Revista: AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volumen: 295
Número: 5
Editorial: AMER PHYSIOLOGICAL SOC
Fecha de publicación: 2008
Página de inicio: G1058
Página final: G1067
Idioma: English
URL: http://ajpgi.physiology.org/cgi/doi/10.1152/ajpgi.90384.2008
DOI:

10.1152/ajpgi.90384.2008

Notas: ISI, SCOPUS