Although neural modulation of heart rate is well established among chordate animals, the Pacific hagfish (Eptatretus stoutii) lacks any cardiac innervation, yet it can increase its heart rate from the steady, depressed heart rate seen in prolonged anoxia to almost double its normal normoxic heart rate, an almost fourfold overall change during the 1-h recovery from anoxia. The present study sought mechanistic explanations for these regulatory changes in heart rate. We provide evidence for a bicarbonate-activated, soluble adenylyl cyclase (sAC)-dependent mechanism to control heart rate, a mechanism never previously implicated in chordate cardiac control.
The authors declare no competing or financial interests.
C.M.W. was involved in study conception and design, carried out all experiments with live animals and isolated hearts, contributed to the sAC biochemical experiments and produced the first draft of the manuscript. J.N.R. performed most of the sAC and NBC biochemical and microscopy experiments. G.K.C. conducted the plasma bicarbonate measurements. M.T. designed the biochemical and microscopy portion of the study and contributed to the microscopy experiments. A.P.F. was involved in study conception and design. All authors analyzed the data, critically assessed and revised the manuscript, and gave final approval for publication.
J.N.R. is supported by a Porter Fellowship from the American Physiological Society. M.T. is supported by the National Science Foundation [grant IOS 1354181] and an Alfred P. Sloan Foundation Research Fellowship [BR2013-103]. A.P.F. is supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada, and the Canada Research Chairs.
- Received January 28, 2016.
- Accepted August 2, 2016.
- © 2016. Published by The Company of Biologists Ltd