NaBC1 was previously postulated to stimulate cell growth and proliferation by increasing intracellular borate and activating the mitogen activated protein kinase pathway.
16 However, a role for borate has not been clearly demonstrated in humans.
10 As borate can diffuse across biological membranes as an uncharged molecule at physiological pH, the requirement for an active transporter for borate is also not evident.
10,16,28 Moreover, recent in vitro studies have shown that the human NaBC1 does not have borate transporter activity. Ogando et al. (Ogando DG, et al.
IOVS 2012;53:ARVO E-Abstract 6005) demonstrated that NaBC1 is a transporter with Na
+:OH
− cotransport activity and not a bicarbonate transporter or a borate-linked cotransporter. Accumulation of NaCl in the corneal stroma of the
Slc4a11 KO mice generated by Gröger et al.
26 was attributed to the failure of fluid transport from the corneal endothelium that is coupled to transcellular solute movement.
8,26,29 Slc4a11 is also expressed in the inner ear and kidney, and studies have demonstrated defects of these organs in other mouse models (i.e., sensorineural hearing loss and urinary concentrating defects).
25,26,30 The results of urine analyses showed significantly decreased urine osmolarity and electrolyte concentrations in the KO mice, suggesting impaired water resorption in the kidney. However, although the
SLC4A11 gene is expressed in human kidney,
13 the phenotypic change in human kidney has never been extensively studied. Vilas et al.
18 showed that NaBC1 mediates water movement across the basolateral surface of endothelium, working in concert with apical aquaporin proteins.
18 However, they suggested that the only driving force for water flux is osmotic gradient, and that it was not coupled to solute movement.