Differential effects of bicarbonate on severe hypoxia- and hypercapnia-induced cardiac malfunctions in diverse fish species.

We tested in six fish species [Pacific lamprey (Lampetra richardsoni), Pacific spiny dogfish (Squalus suckleyi), Asian swamp eel (Monopterus albus), white sturgeon (Acipenser transmontanus), zebrafish (Danio rerio), and starry flounder (Platichthys stellatus)] the hypothesis that elevated extracellular [HCO] protects spontaneous heart rate and cardiac force development from the known impairments that severe hypoxia and hypercapnic acidosis can induce. Hearts were exposed in vitro to either severe hypoxia (~ 3% of air saturation), or severe hypercapnic acidosis (either 7.5% CO or 15% CO), which reduced heart rate (in six test species) and net force development (in three test species). During hypoxia, heart rate was restored by [HCO] in a dose-dependent fashion in lamprey, dogfish and eel (EC = 5, 25 and 30 mM, respectively), but not in sturgeon, zebrafish or flounder. During hypercapnia, elevated [HCO] completely restored heart rate in dogfish, eel and sturgeon (EC = 5, 25 and 30 mM, respectively), had a partial effect in lamprey and zebrafish, and had no effect in flounder. Elevated [HCO], however, had no significant effect on net force of electrically paced ventricular strips from dogfish, eel and flounder during hypoxia and hypercapnia. Only in lamprey hearts did a specific soluble adenylyl cyclase (sAC) inhibitor, KH7, block the HCO-mediated rescue of heart rate during both hypoxia and hypercapnia, and was the only species where we conclusively demonstrated sAC activity was involved in the protective effects of HCO on cardiac function. Our results suggest a common HCO-dependent, sAC-dependent transduction pathway for heart rate recovery exists in cyclostomes and a HCO-dependent, sAC-independent pathway exists in other fish species.