Because this histochemical difference may indicate a difference in the secretory mechanisms, and as the rabbit is a widely used model for studying the phenomenon of dry eye associated with the disease keratoconjunctivitis sicca,
11 we investigated the nature of the ion channels in the superior lacrimal gland of the rabbit. In an earlier study
12 of rabbit superior lacrimal gland (RSLG) cells, we showed that TEA-sensitive K
+ currents comprises a significant portion of the outward currents. In the present study, the other TEA-insensitive component of outward currents was carried by an outwardly rectifying chloride channel (Cl
OR). Our identification of Cl
OR was based on functional studies, since only a limited number of chloride channel genes have been identified.
13 From the functional point of view, Cl
− channels have been classified according to their gating mechanisms,
14 which include (1) transmembrane voltage (the CLC family), (2) protein kinase or nucleotide mediated mechanism (CFTR), (3) an increase in intracellular Ca
2+ (Ca
2+-activated Cl
− channels, CaCC), (4) cell swelling (volume-regulated anion channels, VRAC), or (5) binding of a ligand (GABA-activated channels). Transepithelial movement of chloride ions in many secretory epithelia may occur through any of four general classes of Cl
− channels based on their modes of activation, including intracellular cAMP, cell swelling (volume changes), hyperpolarization, and intracellular Ca
2+ ([Ca
2+]
i) levels.
14 There most likely is some overlap of function, since apical Cl
− channels that are involved in fluid and electrolyte secretion are primarily activated by cAMP in some epithelia
15 and by Ca
2+ in other epithelia.
16 Also, volume sensitive Cl
− channels have been identified in rat parotid cells
16 and in rat lacrimal gland acinar cells.
17 The voltage-gated Cl
− channel known as CLC-2 is activated by hyperpolarization and is found in a variety of secretory epithelia including mouse mandibular cells
18 and rat parotid acinar cells.
16 The rat submandibular gland cells
17 and the rat lacrimal gland cells
19 were found to express CLC-3 protein and contain mRNA for CLC-3 which has a controversial role as mediating a swelling-induced Cl
− current.
13 We investigated the hypothesis that the Cl
OR channels that we identified in the RSLG acini may have a role in regulating the volume of lacrimal acinar cells, since it has been shown that salivary acinar cells undergo changes in volume during secretion.
20