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The Role of the Voltage-Sensitive Release Mechanism in Contraction of Normal and Diseased Heart

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Signal Transduction and Cardiac Hypertrophy

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 7))

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Summary

The series of events which couple depolarisation of the cardiac cell membrane to initiation of contraction are known as excitation-contraction coupling (EC-coupling). A key event in EC-coupling is the release of Ca2+ from stores in the sarcoplasmic reticulum (SR). Until recently, it was believed that release of SR Ca2+ in heart could be triggered only by a process called Ca2+-induced Ca2+ release (CICR). However, recent studies have demonstrated an additional separate mechanism which initiates release of SR Ca2+ independently of conventional CICR. This new mechanism, called the voltage-sensitive release mechanism (VSRM), contributes substantially to initiation of contraction and to changes in magnitude of contraction with changes in heart rate. Furthermore, the VSRM is a target for several major signalling pathways, which indicates that it may play a major role in regulation of the strength of cardiac contraction. The VSRM also may play an important role in contractile dysfunction accompanying heart disease, as the VSRM is selectively depressed in at least two models of heart failure. The mechanism by which the VSRM releases Ca2+ from the SR is currently the subject o f experimental research, which may provide new targets for therapeutic actions to improve contractile function in heart disease.

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References

  1. Fabiato A. 1985. Rapid ionic modifications during the aequorin-detected calcium transient in a skinned canine cardiac Purkinje cell. J Gen Physiol 85:189–246.

    Article  PubMed  CAS  Google Scholar 

  2. Fabiato A. 1985. Time and calcium dependence of activation and inactivation of calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell. J Gen Physiol 85:247–290.

    Article  PubMed  CAS  Google Scholar 

  3. Fabiato A. 1985. Simulated calcium current can both cause calcium loading in and trigger calcium release from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell. J Gen Physiol 85:291–320.

    Article  PubMed  CAS  Google Scholar 

  4. Barcenas-Ruiz L, Wier WG. 1987. Voltage dependence of intracellular [Ca2+]i transients in guineapig ventricular myocytes. Circ Res 61:148–154.

    Article  PubMed  CAS  Google Scholar 

  5. Beuckelmann DJ, Wier WG. 1988. Mechanism of release of calcium from sarcoplasmic reticulum of guinea-pig cardiac cells. J Physiol (Lond) 405:233–255.

    PubMed  CAS  Google Scholar 

  6. Cleemann L, Morad M. 1991. Role of Ca2+ channel in cardiac excitation-contraction coupling in the rat: evidence from Ca2+ transients and contraction. J Physiol (Lond) 432:283–312.

    PubMed  CAS  Google Scholar 

  7. duBell WH, Houser SR. 1989. Voltage and beat dependence of the Ca2+ transient in feline ventricular myocytes. Am J Physiol 257:H746–H759.

    Google Scholar 

  8. London B, Krueger JW. 1986. Contraction in voltage-clamped, internally perfused single heart cells. J Gen Physiol 88:475–505.

    Article  PubMed  CAS  Google Scholar 

  9. Nabauer M, Callewaert G, Cleemann L, Morad M. 1989. Regulation of calcium release is gated by calcium current, not gating charge, in cardiac myocytes. Science 244:800–803.

    Article  PubMed  CAS  Google Scholar 

  10. Ferrier GR, Redondo IM, Mason CA, Mapplebeck CL, Howlett SE. 2000. Regulation of contraction and relaxation by membrane potential in cardiac ventricular myocytes. Am J Physiol 278: H1618–H1626.

    Google Scholar 

  11. Howlett SE, Zhu JQ, Ferrier GR. 1998. Contribution of a voltage-sensitive calcium release mechanism to contraction in cardiac ventricular myocytes. Am J Physiol 274:H155–H170.

    Google Scholar 

  12. Bers DM. 2001. Excitation-Contraction Coupling and Cardiac Contractile Force, 2nd Edition. Dordrecht, The Netherlands: Kluwer Academic Publishers, 2001.

    Book  Google Scholar 

  13. Hobai IA, Howarth FC, Pabbathi VK, Dalton GR, Hancox J C, Zhu JQ, Howlett SE, Ferrier GR, Levi AJ. 1997. “Voltage-activated Ca release” in rabbit, rat and guinea-pig cardiac myocytes, and modulation by internal cAMP. Pflugers Arch 435:164–173.

    Article  PubMed  CAS  Google Scholar 

  14. Ferrier GR, Howlett SE. 1995. Contractions in guinea-pig ventricular myocytes triggered by a calcium-release mechanism separate from Na+ and L-currents. J Physiol (Lond) 484:107–122.

    PubMed  CAS  Google Scholar 

  15. Howlett SE, Ferrier GR. 1997. The voltage-sensitive release mechanism: a new trigger for cardiac contraction. Can J Physiol 75:1044–1057.

    Article  CAS  Google Scholar 

  16. Ferrier GR, Zhu JQ, Redondo IM, Howlett SE. 1998. A role for cAMP dependent kinase A in activation of the voltage-sensitive release mechanism for cardiac contraction. J Physiol (Lond) 513:185–201.

    Article  PubMed  CAS  Google Scholar 

  17. Zhu JQ, Ferrier GR. 2000. Regulation of a voltage-sensitive release mechanism by Ca2+-calmodulin dependent kinase in cardiac myocytes. Am J Physiol 279:H2104–H2115.

    Google Scholar 

  18. Howlett SE, Ferrier GR. 2001. Cardiac excitation-contraction coupling: role of membrane potential in regulation of contraction. Am J Physiol 280:H1928–H1944.

    Google Scholar 

  19. Emanuel K, Mackiewicz U, Lewartowski B. 2001. On the source of Ca2+ activating the tonic component of contraction of myocytes of guinea pig heart. Cardiovasc Res 52:76–83.

    Article  PubMed  CAS  Google Scholar 

  20. Sham JS, Song LS, Chen Y, Deng LH, Stern MD, Lakatta EG, Cheng H. 1998. Termination of Ca2+ release by a local inactivation of ryanodine receptors in cardiac myocytes. Proc Natl Acad Sci USA 95:15096–15101.

    Article  PubMed  CAS  Google Scholar 

  21. Howlett SE, Xiong W, Mapplebeck C, Ferrier GR. 1999. Role of the voltage-sensitive release mechanism in depression of cardiac contraction in myopathic hamsters. Am J Physiol 277:H1690-H1700.

    PubMed  CAS  Google Scholar 

  22. Mason CA, Ferrier GR. 1999. Tetracaine can inhibit contractions initiated by a voltage-sensitive release mechanism in guinea pig ventricular myocytes. J Physiol (Lond) 519:851–865.

    Article  PubMed  CAS  Google Scholar 

  23. Mackiewicz U, Emanuel K, Lewartowski B. 2000. Dihydropyridine receptors functioning as voltage sensors in cardiac myocytes. J Physiol Pharmacol 51:777–798.

    PubMed  CAS  Google Scholar 

  24. McDonald TF, Pelzer S, Trautwein W, Pelzer DJ. 1994. Regulation and modulation of calcium channels in cardiac, skeletal, and smooth muscle cells. Physiol Rev 74:365–507.

    PubMed  CAS  Google Scholar 

  25. Hadley RW, LedererWJ. 1995. Nifedipine inhibits movement of cardiac calcium channels through late, but not early, gating transitions. Am J Physiol 269:H1784–H1790.

    Google Scholar 

  26. Katzung B. 2001. Basic and Clinical Pharmacology, 8th edition. New York: McGraw-Hill.

    Google Scholar 

  27. Overend CL, Eisner DA, O’Neill SC. 1997. The effect of tetracaine on spontaneous Ca2+ release and sarcoplasmic reticulum Ca2+ content in rat ventricular myocytes. J Physiol (Lond) 502:471–479.

    Article  PubMed  CAS  Google Scholar 

  28. Overend CL, O’Neill SC, Eisner DA. 1998. The effect of tetracaine on stimulated contractions, sarcoplasmic reticulum Ca2+ content and membrane current in isolated rat ventricular myocytes. J Physiol (Lond) 507:759–769.

    Article  PubMed  CAS  Google Scholar 

  29. Meissner G. 1986. Ryanodine activation and inhibition of the Ca2+ release channel of sarcoplasmic reticulum. J Biol Chem 261:6300–6306.

    PubMed  CAS  Google Scholar 

  30. Rousseau E, Smith JS, Meissner G. 1987. Ryanodine modifies conductance and gating behavior of single Ca++ release channel. Am J Physiol 253:C364–C368.

    Google Scholar 

  31. Shattock JM, Bers DM. 1987. Inotropic response to hypothermia and the temperature-dependence of ryanodine action in isolated rabbit and rat ventricular muscle: implications for excitation-contraction coupling. Circ Res 61:761–771.

    Article  PubMed  CAS  Google Scholar 

  32. Mason CA, Howlett SE, Ferrier GR. 1998. Ryanodine selectively inhibits the voltage-sensitive release mechanism for SR Ca in guinea-pig ventricular myocytes. Biophys J 74:A55.

    Google Scholar 

  33. Xiong W, Moore HM, Howlett SE, Ferrier GR. 2001. In contrast to forskolin and 3-isobutylmethylxanthine, amrinone stimulates the cardiac voltage sensitive release mechanism without increasing calcium-induced calcium release. J Pharmacol Exp Ther 298:1–10.

    Google Scholar 

  34. Howlett SE, Ferrier GR. 2002. Differential effects of specific phosphodiesterase (PDE) III and IV inhibition on contraction in cardiac myocytes. Biophys J 82:67a.

    Google Scholar 

  35. Housley MD, Milligan G. 1997. Tailoring cAMP signalling responses through isoform multiplicity. Trends Biol Sci 22:217–224.

    Article  Google Scholar 

  36. McCartney S, Little BM, Langeberg LK, Scott JD. 1995. Cloning and characterization of A-kinase anchor protein 100 (AKAP100). A protein that targets A-kinase to the sarcoplasmic reticulum. J Biol Chem 270:9327–9333.

    Article  PubMed  CAS  Google Scholar 

  37. Meyer RB, Miller JP. 1974. Analogs of cyclic AMP and cyclic GMP: general methods of synthesis and the relationship of structure’to enzymic activity. Life Sci 14:1019–1040.

    Article  PubMed  CAS  Google Scholar 

  38. Ferrier GR, Redondo IM, Zhu JQ, Howlett SE. 2000. A critical role for phosphodiesterase in regulation of the cardiac voltage-sensitive release mechanism (VSRM) by cAMP analogs in whole cell voltage clamp investigations. Biophys J 78:371A.

    Google Scholar 

  39. Piacentino V, Dipla K, Gaughan JP, Houser SR. 2000. Voltage-dependent Ca2+ release from the SR of feline ventricular myocytes is explained by Ca2+-induced Ca2+ release. J Physiol (Lond) 523:533–548.

    Article  PubMed  CAS  Google Scholar 

  40. Felix CA, Howlett SE, Ferrier GR. 2002. Muscarinic agonists modulate the cardiac voltage-sensitive release mechanism (VSRM) in the absence of adrenergic stimulation. Biophys J 82:67a.

    Google Scholar 

  41. Ferrier GR, Redondo IM. 1996. Low temperature inhibits cardiac contractions initiated by the voltage-sensitive release mechanism. J Mol Cell Cardiol 28:A180.

    Google Scholar 

  42. Miyamoto S, Hori M, Izumi M, Ozaki H, Karaki H. 2001. Species- and temperature-dependency of the decrease in myofilament Ca2+ sensitivity induced by beta-adrenergic stimulation. Jpn J Pharmacol 85:75–83.

    Article  PubMed  CAS  Google Scholar 

  43. Zhu JQ, Ferrier GR. 1999. Role of the voltage-sensitive release mechanism in force-interval relations and staircases in cardiac ventricular myocytes. Biophys J 76:A458.

    Article  Google Scholar 

  44. Bowditch HP. 1871. Über die Eigenthümlichkeiten der Reizbarkeit, welche die Muskelfasern des Herzens zeigen. Ber. Sächs. Akad. Wiss. 23:652–689.

    Google Scholar 

  45. Koch-Weser J, Blinks J R. 1963. The influence of the interval between beats on myocardial contractility. Pharmacol Rev 15:601–651.

    PubMed  CAS  Google Scholar 

  46. Sjaastad I, Birkeland JA, Ferrier GR, Howlett SE, Wasserstrom JA, Sejersted OM. 2000. Rats with congestive heart failure exhibit a defect in excitation-contraction coupling caused by suppression of the voltage sensitive release mechanism. Circ 102:II–297.

    Google Scholar 

  47. Frank K, Kranias EG. 2000. Phospholamban and cardiac contractility. Ann Med 32:572–578.

    Article  PubMed  CAS  Google Scholar 

  48. Wang X, Dhalla NS. 2000. Modification of beta-adrenoceptor signal transduction pathway by genetic manipulation and heart failure. Mol Cell Biochem 214:131–155.

    Article  PubMed  CAS  Google Scholar 

  49. Katoh H, Schlotthauer K, Bers DM. 2000. Transmission of information from cardiac dihydropyridine receptor to ryanodine receptor: evidence from Bay K 8644 effects on resting Ca2+ sparks. Circ Res 87:106–111.

    Article  PubMed  CAS  Google Scholar 

  50. Li Y, Bers DM. 2001. A cardiac dihydropyridine receptor II—III loop peptide inhibits resting Ca2+ sparks in ferret ventricular myocytes. J Physiol (Lond) 537:17–26.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Cardiovascular Research Laboratories Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada

    Susan E. Howlett & Gregory R. Ferrier

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  1. Susan E. Howlett
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  2. Gregory R. Ferrier
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Correspondence to Susan E. Howlett or Gregory R. Ferrier .

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Editors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director), Larry V. Hryshko PhD (Associate Professor), Elissavet Kardami PhD (Professor) & Pawan K. Singal PhD, DSc (Professor) (Distinguished Professor and Director),  (Associate Professor),  (Professor) &  (Professor)

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Howlett, S.E., Ferrier, G.R. (2003). The Role of the Voltage-Sensitive Release Mechanism in Contraction of Normal and Diseased Heart. In: Dhalla, N.S., Hryshko, L.V., Kardami, E., Singal, P.K. (eds) Signal Transduction and Cardiac Hypertrophy. Progress in Experimental Cardiology, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0347-7_16

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  • DOI: https://doi.org/10.1007/978-1-4615-0347-7_16

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5032-3

  • Online ISBN: 978-1-4615-0347-7

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