Connexin 37 contributes to water homeostasis and urinary concentrating ability

Abstract

Connexin 37 (Cx37) is one gap junction component which plays an important role in intercellular communication. In the kidney, multiple gap junction proteins have been localized including Cx37. Previous studies have shown that Cx37 is expressed in a punctate pattern in the renal vasculature and along the nephron. Regarding the latter, strong basolateral expression was found in the thick ascending limb and distal convoluted tubule, weaker expression was found in the proximal tubule and collecting duct. Functional data are limited, with one study implying a role of Cx37 in sodium homeostasis. Based on its localization, we hypothesized that Cx37 possibly contributes to fluid homeostasis. In order to gain further insight, we studied wild‐type (WT, n=9–12) and Cx37 knockout mice (Cx37−/−, n=9–12). Under baseline conditions, Cx37−/− showed a ~40% higher fluid intake (5.7±0.3 vs 4.2±0.3 mL/day, P<0.05) associated with a ~40% lower urine osmolality (1611±79 vs 2556±171 mOsm/kg, P<0.05) compared to WT mice. Plasma osmolality (Cx37−/−: 333±2 vs WT: 334±2 mOsm/kg, NS) and food intake (Cx37−/−: 4.0±0.2 vs WT: 3.7±0.2 g/day, NS) were not significantly different between genotypes indicating that Cx37−/− mice are in fluid balance. To determine the role of Cx37 in the urinary concentrating mechanism, we conducted 18‐hour water deprivation studies. In response to water deprivation, urine osmolality increased significantly in both groups but the increase remained ~375 mOsm/kg lower in Cx37−/− vs WT mice (3355±85 vs 3730±181 mOsm/kg, P<0.05), an effect associated with a more pronounced body weight loss (8.8±0.6 vs 7.2±0.5%, P<0.05) indicative of greater urinary water loss. The increase in plasma osmolality was not significantly different between Cx37−/− and WT mice (Δ change: 14±3 vs 11±2 mOsm/kg, NS). Consistent with greater thirst, fluid intake in the first 6 hours after water deprivation was significantly greater in Cx37−/− vs WT mice (4.1±0.4 vs 3.0±0.3 mL, P<0.05). In summary, these results demonstrate that expression of Cx37 is important for urinary concentration in vivo, including in response to water restriction.Support or Funding InformationTR is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK110621). JX was supported by an American Heart Association Predoctoral Fellowship (18PRE33990236) and LT by a Postdoctoral Fellowship (19POST34400026).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.