Dropping the base: recovery from extreme hypercarbia in the CO2 tolerant Pacific hagfish (Eptatretus stoutii).

Hagfish are capable of tolerating extreme hypercapnia (> 30 Torr) by mounting substantial plasma [HCO3-] (hypercarbia) to compensate for CO2-mediated acidosis. The goal of this study was to characterize the mechanistic hypercarbia-recovery strategies in the highly CO2 tolerant hagfish. We exposed hagfish to hypercapnia (30 Torr) for 48 h and allowed a 24 h recovery period in normocapnic seawater. Within 8 h of the recovery period, the compensatory plasma [HCO3-] load (~ 70 mmol L-1) was rapidly offloaded. While increases in both whole-animal HCO3- excretion and glomerular filtration were observed throughout recovery (2-8 h), neither can fully account for the observed rates of whole-animal HCO3- loss, which peaked at ~ 3.5 mmol kg-1 h-1. Inhibition of carbonic anhydrase via acetazolamide revealed that the restoration of plasma [HCO3-] from hypercapnia-induced hypercarbia is likely facilitated in a dualistic manner, initially relying on both carbonic anhydrase mediated CO2 offloading and Cl-/HCO3- exchange processes, both of which are likely either upregulated or further activated as recovery progresses.