Fish Physiology and Biochemistry

, Volume 40, Issue 2, pp 539–549 | Cite as

Species- and chamber-specific responses of 12 kDa FK506-binding protein to temperature in fish heart

  • Hanna Korajoki
  • Matti Vornanen


The sarcoplasmic reticulum (SR) Ca2+ release channel or ryanodine receptor (RyR) of the vertebrate heart is regulated by the FK506-binding proteins, FKBP12 and FKBP12.6. This study examines whether temperature-related changes in the SR function of fish hearts are associated with changes in FKBP12 expression. For this purpose, a polyclonal antibody against trout FKBP12 was used to compare FKPB12 expression in cold-acclimated (4 °C, CA) and warm-acclimated (18 °C, WA) rainbow trout (Oncorhynchus mykiss), burbot (Lota lota) and crucian carp (Carassius carassius) hearts. FKBP12 expression was modulated in a species- and tissue-specific manner. Temperature acclimation affected FKBP12 expression only in atrial tissue. Changes in the ventricular FKBP12 expression were not detected in any of the fish species. In the atria of rainbow trout and crucian carp, temperature acclimation produced opposite thermal responses: FKBP12 increased in the trout atrium and decreased in the crucian carp atrium under cold acclimation. In the burbot heart, chronic temperature changes did not affect cardiac FKBP12 levels. Expression of FKBP12 mRNA in rainbow trout and crucian carp hearts suggests that the transcript levels are higher in the ventricle than in the atrium and are elevated by cold acclimation in trout, but not in crucian carp. Since FKBP12 is known to increase the Ca2+ sensitivity of cardiac RyRs and thereby the opening frequency of the Ca2+ release channels, temperature-related changes in FKBP12 expression may modify the SR function in excitation–contraction coupling. The cold-induced increase in FKBP12 in the trout atrium and decrease in the crucian carp atrium are consistent with the previously noted increase and decrease, respectively, of SR Ca2+ stores in cardiac contraction in these species.


Calcium-induced calcium release Thermal acclimation Fish heart Excitation–contraction coupling Sarcoplasmic reticulum 



Skillful technical assistance of Anita Kervinen and Riitta Pietarinen is acknowledged. This research was supported by a Grant from The Academy of Finland (127192) to M.V.


  1. Aho E, Vornanen M (1998) Ca2+ -ATPase activity and Ca2+ uptake by sarcoplasmic reticulum in fish heart: effects of thermal acclimation. J Exp Biol 201:525–532PubMedGoogle Scholar
  2. Aho E, Vornanen M (1999) Contractile properties of atrial and ventricular myocardium of the heart of rainbow trout Oncorhynchus mykiss: effects of thermal acclimation. J Exp Biol 202(Pt 19):2663–2677PubMedGoogle Scholar
  3. Birkedal R, Christopher J, Thistlethwaite A, Shiels HA (2009) Temperature acclimation has no effect on ryanodine receptor expression or subcellular localization in rainbow trout heart. J Comp Physiol B 179:961–969PubMedCrossRefGoogle Scholar
  4. Bowler K, Tirri R (1990) Temperature dependence of the heart isolated from the cold or warm acclimated perch (Perca fluviatilis). Comp Biochem Physiol A 96:177–180CrossRefGoogle Scholar
  5. Chelu MG, Danila CI, Gilman CP, Hamilton SL (2004) Regulation of ryanodine receptors by FK506 binding proteins. Trends Cardiovasc Med 14:227–234PubMedCrossRefGoogle Scholar
  6. Driedzic W, Gesser H (1988) Differences in force-frequency relationships and calcium dependency between elasmobranch and teleost hearts. J Exp Biol 140:227–241Google Scholar
  7. Galfre E, Pitt SJ, Venturi E, Sitsapesan M, Zaccai NR, Tsaneva-Atanasova K, O’Neill S, Sitsapesan R (2012) FKBP12 activates the cardiac ryanodine receptor Ca2+-release channel and is antagonised by FKBP12.6. PLoS One 7:e31956PubMedCentralPubMedCrossRefGoogle Scholar
  8. Gesser H (1996) Cardiac force-interval relationship, adrenaline and sarcoplasmic reticulum in rainbow trout. J Comp Physiol B 166:278–285CrossRefGoogle Scholar
  9. Gillis TE, Klaiman JM (2011) The influence of PKA treatment on the Ca2+ activation of force generation by trout cardiac muscle. J Exp Biol 214:1989–1996PubMedCrossRefGoogle Scholar
  10. Gillis TE, Marshall CR, Xue XH, Borgford TJ, Tibbits GF (2000) Ca2+ binding to cardiac troponin C: effects of temperature and pH on mammalian and salmonid isoforms. Am J Physiol Regul Integr Comp Physiol 279:R1707–R1715PubMedGoogle Scholar
  11. Guo T, Cornea RL, Huke S, Camors E, Yang Y, Picht E, Fruen BR, Bers DM (2010) Kinetics of FKBP12.6 binding to ryanodine receptors in permeabilized cardiac myocytes and effects on Ca sparks. Circ Res 106:1743–1752PubMedCentralPubMedCrossRefGoogle Scholar
  12. Gyorke S, Terentyev D (2008) Modulation of ryanodine receptor by luminal calcium and accessory proteins in health and cardiac disease. Cardiovasc Res 77:245–255PubMedCrossRefGoogle Scholar
  13. Hassinen M, Paajanen V, Haverinen J, Eronen H, Vornanen M (2007) Cloning and expression of cardiac Kir2.1 and Kir2.2 channels in thermally acclimated rainbow trout. Am J Physiol Regul Integr Comp Physiol 292:R2328–R2339PubMedCrossRefGoogle Scholar
  14. Hassinen M, Paajanen V, Vornanen M (2008) A novel inwardly rectifying K+ channel, Kir2.5, is upregulated under chronic cold stress in fish cardiac myocytes. J Exp Biol 211:2162–2171PubMedCrossRefGoogle Scholar
  15. Haverinen J, Vornanen M (2009a) Comparison of sarcoplasmic reticulum calcium content in atrial and ventricular myocytes of three fish species. Am J Physiol Regul Integr Comp Physiol 297:R1180–R1187PubMedCrossRefGoogle Scholar
  16. Haverinen J, Vornanen M (2009b) Responses of action potential and K+ currents to temperature acclimation in fish hearts: phylogeny or thermal preferences? Physiol Biochem Zool 82:468–482PubMedCrossRefGoogle Scholar
  17. Hove-Madsen L (1992) The influence of temperature on ryanodine sensitivity and the force-frequency relationship in the myocardium of rainbow trout. J Exp Biol 167:47PubMedGoogle Scholar
  18. Hove-Madsen L, Llach A, Tort L (1998) Quantification of Ca2+ uptake in the sarcoplasmic reticulum of trout ventricular myocytes. Am J Physiol 275:R2070–R2080PubMedGoogle Scholar
  19. Hove-Madsen L, Llach A, Tort L (1999) Quantification of calcium release from the sarcoplasmic reticulum in rainbow trout atrial myocytes. Pflugers Arch 438:545–552PubMedCrossRefGoogle Scholar
  20. Jeyakumar LH, Ballester L, Cheng DS, McIntyre JO, Chang P, Olivey HE, Rollins-Smith L, Barnett JV, Murray K, Xin HB, Fleischer S (2001) FKBP binding characteristics of cardiac microsomes from diverse vertebrates. Biochem Biophys Res Commun 281:979–986PubMedCrossRefGoogle Scholar
  21. Jiang D, Wang R, Xiao B, Kong H, Hunt DJ, Choi P, Zhang L, Chen SRW (2005) Enhanced store overload–induced Ca2+ release and channel sensitivity to luminal Ca2+ activation are common defects of RyR2 mutations linked to ventricular tachycardia and sudden death. Circ Res 97:1173–1181PubMedCrossRefGoogle Scholar
  22. Keen JE, Vianzon D, Farrell AP, Tibbits GF (1994) Effect of temperature and temperature acclimation on the ryanodine sensitivity of the trout myocardium. J Comp Physiol B 164:438–443CrossRefGoogle Scholar
  23. Korajoki H, Vornanen M (2009) Expression of calsequestrin in atrial and ventricular muscle of thermally acclimated rainbow trout. J Exp Biol 212:3403–3414PubMedCrossRefGoogle Scholar
  24. Korajoki H, Vornanen M (2012) Expression of SERCA and phospholamban in rainbow trout (Oncorhynchus mykiss) heart: comparison of atrial and ventricular tissue and effects of thermal acclimation. J Exp Biol 215:1162–1169PubMedCrossRefGoogle Scholar
  25. Korajoki H, Vornanen M (2013) Temperature dependence of sarco (endo)plasmic reticulum Ca2+ ATPase expression in fish hearts. J Comp Physiol B 183:467–476PubMedCrossRefGoogle Scholar
  26. Kushnir A, Marks AR (2010) The ryanodine receptor in cardiac physiology and disease. Adv Pharmacol 59:1–30PubMedCentralPubMedCrossRefGoogle Scholar
  27. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685PubMedCrossRefGoogle Scholar
  28. Lam E, Martin MM, Timerman AP, Sabers C, Fleischer S, Lukas T, Abraham RT, O’Keefe SJ, O’Neill EA, Wiederrecht GJ (1995) A novel FK506 binding protein can mediate the immunosuppressive effects of FK506 and is associated with the cardiac ryanodine receptor. J Biol Chem 270:26511–26522PubMedCrossRefGoogle Scholar
  29. Lanner JT, Georgiou DK, Joshi AD, Hamilton SL (2010) Ryanodine receptors: structure, expression, molecular details, and function in calcium release. Cold Spring Harb Perspect Biol 2:a003996PubMedCentralPubMedCrossRefGoogle Scholar
  30. Shiels HA, Stevens ED, Farrell AP (1998) Effects of temperature, adrenaline and ryanodine on power production in rainbow trout oncorhynchus mykiss ventricular trabeculae. J Exp Biol 201(Pt 19):2701–2710PubMedGoogle Scholar
  31. Shiels HA, Freund EV, Farrell AP, Block BA (1999) The sarcoplasmic reticulum plays a major role in isometric contraction in atrial muscle of yellowfin tuna. J Exp Biol 202(Pt 7):881–890PubMedGoogle Scholar
  32. Shiels HA, Vornanen M, Farrell AP (2002a) The force-frequency relationship in fish hearts—a review. Comp Biochem Physiol A Mol Integr Physiol 132:811–826PubMedCrossRefGoogle Scholar
  33. Shiels HA, Vornanen M, Farrell AP (2002b) Effects of temperature on intracellular Ca2+ in trout atrial myocytes. J Exp Biol 205:3641–3650PubMedGoogle Scholar
  34. Shiels HA, Di Maio A, Thompson S, Block BA (2011) Warm fish with cold hearts: thermal plasticity of excitation–contraction coupling in bluefin tuna. Proc Biol Sci 278:18–27PubMedCentralPubMedCrossRefGoogle Scholar
  35. Tibbits GF, Moyes CD, Hove-Madsen L (1992) Excitation-contraction coupling in the teleost heart. In: Hoar WS, Randall DJ, Farrell AP (eds) Fish physiology volume XII, part A, the cardiovascular system. Academic Press, San Diego, pp 267–304Google Scholar
  36. Tiitu V, Vornanen M (2001) Cold adaptation suppresses the contractility of both atrial and ventricular muscle of the crucian carp heart. J Fish Biol 59:141–156CrossRefGoogle Scholar
  37. Tiitu V, Vornanen M (2002) Regulation of cardiac contractility in a cold stenothermal fish, the burbot Lota lota L. J Exp Biol 205:1597–1606PubMedGoogle Scholar
  38. Tiitu V, Vornanen M (2003) Ryanodine and dihydropyridine receptor binding in ventricular cardiac muscle of fish with different temperature preferences. J Comp Physiol B 173:285–291PubMedCrossRefGoogle Scholar
  39. Timerman AP, Jayaraman T, Wiederrecht G, Onoue H, Marks AR, Fleischer S (1994) The ryanodine receptor from canine heart sarcoplasmic reticulum is associated with a novel FK-506 binding protein. Biochem Biophys Res Commun 198:701–706PubMedCrossRefGoogle Scholar
  40. Timerman AP, Onoue H, Xin HB, Barg S, Copello J, Wiederrecht G, Fleischer S (1996) Selective binding of FKBP12.6 by the cardiac ryanodine receptor. J Biol Chem 271:20385–20391PubMedCrossRefGoogle Scholar
  41. Vornanen M (1989) Regulation of contractility of the fish (Carassius carassius L.)heart ventricle. Comp Biochem Physiol 94C:477–483Google Scholar
  42. Vornanen M (2006) Temperature and Ca2+ dependence of [3H]ryanodine binding in the burbot (Lota lota L.) heart. Am J Physiol Regul Integr Comp Physiol 290:R345–R351PubMedCrossRefGoogle Scholar
  43. Vornanen M, Shiels HA, Farrell AP (2002) Plasticity of excitation-contraction coupling in fish cardiac myocytes. Comp Biochem Physiol A 132:827–846CrossRefGoogle Scholar
  44. Vornanen M, Hassinen M, Koskinen H, Krasnov A (2005) Steady-state effects of temperature acclimation on the transcriptome of the rainbow trout heart. Am J Physiol Regul Integr Comp Physiol 289:R1177–R1184PubMedCrossRefGoogle Scholar
  45. Vornanen M, Stecyk JA, Nilsson GE (2009) The anoxia-tolerant crucian carp (Carassius carassius L.). In: Richards JG, Farrell AP, Brauner CJ (eds) Hypoxia. Elsevier, Amsterdam, pp 397–441Google Scholar
  46. Zhang PC, Llach A, Sheng XY, Hove-Madsen L, Tibbits GF (2011) Calcium handling in zebrafish ventricular myocytes. Am J Physiol Regul Integr Comp Physiol 300:R56–R66PubMedCrossRefGoogle Scholar
  47. Zissimopoulos S, Seifan S, Maxwell C, Williams AJ, Lai FA (2012) Disparities in the association of the ryanodine receptor and the FK506-binding proteins in mammalian heart. J Cell Sci 125:1759–1769PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of BiologyUniversity of Eastern FinlandJoensuuFinland

Personalised recommendations