Review Cardiac survival in anoxia-tolerant vertebrates: An electrophysiological perspective ☆ Jonathan A.W. Stecyk a, ⁎, Gina L. Galli b , Holly A. Shiels c , Anthony P. Farrell d a Physiology Programme, Department of Molecular Biosciences, University of Oslo, PO Box 1041, N-0316, Oslo, Norway b Hopkins Marine Station of Stanford University, 120 Ocean View Boulevard, Pacific Grove, CA, 93950, USA c Faculty of Life Sciences, The University of Manchester, Core Technology Facility, Second Floor, 46 Grafton St., Manchester M13 9NT, United Kingdom d Faculty of Land and Food Systems and Department of Zoology, University of British Columbia, Vancouver, BC, Canada V6T 1Z4 ABSTRACT ARTICLE INFO Article history: Received 5 March 2008 Received in revised form 31 May 2008 Accepted 31 May 2008 Available online 05 June 2008 Keywords: Action potential Anoxia Carassius carassius Crucian carp Electrophysiology Heart I Ca I K1 I Kr I Na K + channel L-type Ca 2+ channel Na + channel Red-eared slider turtle Temperature Thermal acclimation Trachemys scripta Certain vertebrates, such as freshwater turtles of the genus Chrysemys and Trachemys and crucian carp (Carassius carassius), have anoxia-tolerant hearts that continue to function throughout prolonged periods of anoxia (up to many months) due to successful balancing of cellular ATP supply and demand. In the present review, we summarize the current and limited understanding of the cellular mechanisms underlying this cardiac anoxia tolerance. What emerges is that cold temperature substantially modifies cardiac elec- trophysiology to precondition the heart for winter anoxia. Intrinsic heart rate is slowed and density of sarcolemmal ion currents substantially modified to alter cardiac action potential (AP) characteristics. These changes depress cardiac activity and reduce the energetic costs associated with ion pumping. In contrast, anoxia per se results in limited changes to cardiac AP shape or ion current densities in turtle and crucian carp, suggesting that anoxic modifications of cardiac electrophysiology to reduce ATP demand are not extensive. Additionally, as knowledge of cellular physiology in non-mammalian vertebrates is still in its infancy, we briefly discuss the cellular defense mechanisms towards the acidosis that accompanies anoxia as well as mammalian cardiac models of hypoxia/ischemia tolerance. By examining if fundamental cellular mechanisms have been conserved during the evolution of anoxia tolerance we hope to have provided a framework for the design of future experiments investigating cardiac cellular mechanisms of anoxia survival. © 2008 Elsevier Inc. All rights reserved. Contents 1. Introduction: the anoxia disaster . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 340 2. Cellular strategies of anoxic survival . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341 2.1. Avoiding the anoxia disaster in brain and liver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341 2.2. Cardiac excitation–contraction coupling and ATP demand . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341 2.3. Potential electrophysiological mechanisms to reduce cardiac ATP demand . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342 3. Freshwater turtles: reducing cardiac activity during anoxia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342 3.1. Cardiovascular status and its control during anoxia exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342 3.2. Turtle cardiac electrophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343 4. Crucian carp: sustaining cardiac activity during anoxia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346 4.1. Cardiovascular status and its control during anoxia exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346 4.2. Crucian carp cardiac electrophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346 5. Cold-temperature: preparing the heart for anoxia exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348 5.1. Effects of low temperature on the turtle heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348 5.2. Effects of low temperature on the crucian carp heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349 Comparative Biochemistry and Physiology, Part C 148 (2008) 339–354 ☆ Contribution to the Special Issue of CBP on Chinese Comparative Biochemistry and Physiology presented at or related to the International Conference of Comparative Physiology, Biochemistry and Toxicology and the 6th Chinese Comparative Physiology Conference, October,10–14, 2007, Zhejiang University, Hangzhou, China. ⁎ Corresponding author. E-mail address: jonathan.stecyk@imbv.uio.no (J.A.W. Stecyk). 1532-0456/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.cbpc.2008.05.016 Contents lists available at ScienceDirect Comparative Biochemistry and Physiology, Part C journal homepage: www.elsevier.com/locate/cbpc