Enhanced formation of a HCO3- transport metabolon in exocrine cells of Nhe1-/- mice.
Cl(-) influx across the basolateral membrane is a limiting step in fluid production in exocrine cells and often involves functionally linked Cl(-)/HCO(3)(-) (Ae) and Na(+)/H(+) (Nhe) exchange mechanisms. The dependence of this major Cl(-) uptake pathway on Na(+)/H(+) exchanger expression was examined in the parotid acinar cells of Nhe1(-/-) and Nhe2(-/-) mice, both of which exhibited impaired fluid secretion. No change in Cl(-)/HCO(3)(-) exchanger activity was detected in Nhe2-deficient mice. Conversely, Cl(-)/HCO(3)(-) exchanger activity increased nearly 4-fold in Nhe1-deficient mice, despite only minimal or any change in mRNA and protein levels of the anion exchanger Ae2. Acetazolamide completely blocked the increase in Cl(-)/HCO(3)(-) exchanger activity in Nhe1-null mice suggesting that increased anion exchange required carbonic anhydrase activity. Indeed, the parotid glands of Nhe1(-/-) mice expressed higher levels of carbonic anhydrase 2 (Car2) polypeptide. Moreover, the enhanced Cl(-)/HCO(3)(-) exchange activity was accompanied by an increased abundance of Car2.Ae2 complexes in the parotid plasma membranes of Nhe1(-/-) mice. Anion exchanger activity was also significantly reduced in Car2-deficient mice, consistent with an important role of a putative Car2.Ae2 HCO(3)(-) transport metabolon in parotid exocrine cell function. Increased abundance of this HCO(3)(-) transport metabolon is likely one of the multiple compensatory changes in the exocrine parotid gland of Nhe1(-/-) mice that together attenuate the severity of in vivo electrolyte and acid-base balance perturbations.
Gonzalez-Begne
Mireya
M
Center for Oral Biology, University of Rochester Medical Center, Rochester, New York 14642, USA.
Nakamoto
Tetsuji
T
Nguyen
Ha-Van
HV
Stewart
Andrew K
AK
Alper
Seth L
SL
Melvin
James E
JE
D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D000838:Anions; D001639:Bicarbonates / Q000737:chemistry*; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004573:Electrolytes; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009865:Oocytes / Q000378:metabolism; D010306:Parotid Gland / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D014981:Xenopus / Q000378:metabolism
D000838:Anions; D001639:Bicarbonates; D027682:Cation Transport Proteins; D004573:Electrolytes; D008565:Membrane Proteins; D012333:RNA, Messenger; C490997:Slc9a1 protein, mouse; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D000086:Acetazolamide