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 3 − ] 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 2 or 15% CO 2 ), which reduced heart rate (in six test species) and net force development (in three test species). During hypoxia, heart rate was restored by [HCO 3 − ] in a dose-dependent fashion in lamprey, dogfish and eel (EC 50  = 5, 25 and 30 mM, respectively), but not in sturgeon, zebrafish or flounder. During hypercapnia, elevated [HCO 3 − ] completely restored heart rate in dogfish, eel and sturgeon (EC 50  = 5, 25 and 30 mM, respectively), had a partial effect in lamprey and zebrafish, and had no effect in flounder. Elevated [HCO 3 − ], 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 3 − -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 3 − on cardiac function. Our results suggest a common HCO 3 − -dependent, sAC-dependent transduction pathway for heart rate recovery exists in cyclostomes and a HCO 3 − -dependent, sAC-independent pathway exists in other fish species.