Molecular mechanisms of Cl⁻ transport in fishes: New insights and their evolutionary context

Abstract

With remarkably few exceptions, aquatic vertebrates maintain internal Cl− homeostasis despite strong and sometimes fluctuating Cl− concentration gradients between extracellular fluids and external environments. In this “Perspective,” we discuss recent advances in the understanding of epithelial Cl− transport at the molecular level within key osmoregulatory organs in fishes. New insights into mechanisms for epithelial Cl− transport in basal lineages are highlighted to provide an evolutionary context. We describe Cl− transport processes that employ: cystic fibrosis transmembrane conductance regulator, cation‐chloride cotransporters, voltage‐gated chloride channels, and chloride‐anion exchangers. As the collective understanding of Cl− transport processes continues to expand, investigators are equipped to more precisely characterize how endocrine factors promote hydromineral balance. We, therefore, conclude our discussion by paying special attention to recently defined roles for prolactin and corticosteroids in the regulation of Cl− transport in basal and derived clades.

Tissue and salinity specific Na+/Cl− cotransporter (NCC) orthologues involved in the adaptive osmoregulation of sea lamprey (Petromyzon marinus)

“…With NKCC2 ruled out by the lack of bumetanide sensitivity, any further speculation about the mechanisms facilitating the residual I sc that is NCCb-independent ( i.e., insensitive to indapamide) is beyond the scope of this investigation. Further studies are required to elucidate whether the NKCC2/NCC-independent mechanisms of Cl − absorption, which have been shown in the teleost intestine 28 , are also present in lampreys. It is also possible that indapamide simply did not fully inhibit all NCCb activity, even at the highest tested doses.…”

“…Although these underlying mechanisms for intestinal SW osmoregulation have been elucidated in teleost fishes, whether such molecular mechanisms are present in the lamprey intestine was unknown prior to the present study 28 . Thus, we aimed to functionally characterize the putative molecular pathway for intestinal ion absorption during SW osmoregulation in the sea lamprey ( Petromyzon marinus ).…”

“…The mechanism for luminal Cl − uptake is species- and tissue-dependent but always includes a member of the SLC family of solute-carrying proteins such as NKCC2, NCC, and/or Cl − /HCO 3 − exchanger 25 – 27 . The active transport of Cl − across the intestinal epithelium is associated with high levels of Na + /K + -ATPase (NKA) activity 28 . The basolateral NKA produces favorable electrochemical gradients for the absorption of Cl − via the SLC cotransporters and anion exchangers localized in the apical and basolateral membranes of enterocytes 14 , 20 , 24 .…”

“…In teleost fishes, NKCC2 is the predominant cation-chloride cotransporter that facilitates apical ion absorption in the SW intestine 27 , 28 , 41 . Ion and water uptake by the intestine has been shown to be inhibited by bumetanide, a selective inhibitor of NKCC 20 .…”

Physiology and aquaculture: A review of ion and acid‐base regulation by the gills of fishes

“…Claudin 10 paralogs; Section 5), basolateral NKCC, apical CFTR and basolateral NKA, which energises the system (Figure 3). Increased expression of NKCC (Blondeau‐Bidet et al, 2019; Hiroi & McCormick, 2007; Hiroi et al, 2005; Inokuchi et al, 2017; Nilsen et al, 2007; Tipsmark et al, 2004; Tipsmark, Baltzegar, et al, 2008; Tipsmark, Luckenbach, et al, 2008; Wilson et al, 2007) and CFTR (Hiroi et al, 2005; Inokuchi et al, 2017; Marshall et al, 2018; McCormick et al, 2003; Nilsen et al, 2007; Wilson et al, 2007) has been observed in numerous euryhaline fish species in response to SW acclimation and these proteins are believed to coordinate Cl − secretion by SW ionocytes (Shaughnessy & Breves, 2021). Basolateral NKCC transports Cl − from the blood into the cytosol of SW ionocytes, energised by the Na + gradient established by NKA, and apical CFTR facilitates the movement of Cl − into SW down its electrochemical gradient.…”