Loss of hyperpolarization-activated Cl(-) current in salivary acinar cells from Clcn2 knockout mice.
ClC-2 is localized to the apical membranes of secretory epithelia where it has been hypothesized to play a role in fluid secretion. Although ClC-2 is clearly the inwardly rectifying anion channel in several tissues, the molecular identity of the hyperpolarization-activated Cl(-) current in other organs, including the salivary gland, is currently unknown. To determine the nature of the hyperpolarization-activated Cl(-) current and to examine the role of ClC-2 in salivary gland function, a mouse line containing a targeted disruption of the Clcn2 gene was generated. The resulting homozygous Clcn2(-/-) mice lacked detectable hyperpolarization-activated chloride currents in parotid acinar cells and, as described previously, displayed postnatal degeneration of the retina and testis. The magnitude and biophysical characteristics of the volume- and calcium-activated chloride currents in these cells were unaffected by the absence of ClC-2. Although ClC-2 appears to contribute to fluid secretion in some cell types, both the initial and sustained salivary flow rates were normal in Clcn2(-/-) mice following in vivo stimulation with pilocarpine, a cholinergic agonist. In addition, the electrolytes and protein contents of the mature secretions were normal. Because ClC-2 has been postulated to contribute to cell volume control, we also examined regulatory volume decrease following cell swelling. However, parotid acinar cells from Clcn2(-/-) mice recovered volume with similar efficiency to wild-type littermates. These data demonstrate that ClC-2 is the hyperpolarization-activated Cl(-) channel in salivary acinar cells but is not essential for maximum chloride flux during stimulated secretion of saliva or acinar cell volume regulation.
Nehrke
Keith
K
Center for Oral Biology, Aab Institute of Biomedical Sciences, the Eastman Department of Dentistry, University of Rochester Medical Center, Rochester, New York 14642, USA.
Arreola
Jorge
J
Nguyen
Ha-Van
HV
Pilato
Jodi
J
Richardson
Linda
L
Okunade
Gbolahan
G
Baggs
Raymond
R
Shull
Gary E
GE
Melvin
James E
JE
D000818:Animals; D000090007:CLC-2 Chloride Channels; D018118:Chloride Channels / Q000235:genetics / Q000502:physiology*; D005260:Female; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D012160:Retina / Q000473:pathology; D012463:Saliva / Q000378:metabolism; D012469:Salivary Glands / Q000166:cytology / Q000502:physiology*; D013737:Testis / Q000473:pathology
D000090007:CLC-2 Chloride Channels; D018118:Chloride Channels; C000715428:Clcn2 protein, mouse