© 1996 American Heart Association, Inc.
Articles |
Regulation of Cardiac Ca2+ Release Channel (Ryanodine Receptor) by Ca2+, H+, Mg2+, and Adenine Nucleotides Under Normal and Simulated Ischemic Conditions
the Department of Biochemistry and Biophysics and the Department of Physiology, University of North Carolina, Chapel Hill.
Correspondence to Gerhard Meissner, Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599-7260.
In myocardial ischemia, pHi and [ATP] fall, whereas the free [Ca2+] and [Mg2+] rise. The effects of these changes on cardiac Ca2+ release channel (ryanodine receptor) activity were investigated in [3H]ryanodine binding and single-channel measurements, using isolated membrane and purified channel preparations. In the absence of the two channel ligands Mg2+ and ATP, cardiac Ca2+ release channels were half-maximally activated at pH 7.4 by 
4 µmol/L cytosolic Ca2+ and half-maximally inhibited by 9 mmol/L cytosolic Ca2+. Regulation of channel activity by Ca2+ was modulated by Mg2+ and ATP. Single-channel activities were more sensitive to a change of cytosolic pH than SR lumenal pH. Reduction in lumenal and/or cytosolic pH from 7.3 to 6.5 and 6.0 resulted in decreased single-channel activities without a change in single-channel conductance. [3H]Ryanodine binding measurements also indicated that acidosis impairs cardiac Ca2+ release channel activity. Mg2+ and adenine nucleotide concentrations regulated the extent of inhibition and the Ca2+ dependence of binding. In the presence of 5 mmol/L Mg2+ and 5 mmol/L ß,
-methyleneadenosine 5'-triphosphate (AMPPCP, a nonhydrolyzable ATP analogue), the free [Ca2+] for half-maximal [3H]ryanodine binding was increased from 1.9 µmol/L at pH 7.3 to 36 µmol/L at pH 6.5 and to 89 µmol/L at pH 6.2. These results suggest that ionic and metabolic changes that might be expected to affect sarcoplasmic reticulum Ca2+ release channel activity in ischemic myocardium include an altered Ca2+ sensitivity of the channel, a fall in pH, and a loss of the high-energy adenine nucleotide pool, leading to an increased inhibition by Mg2+.
Key Words: excitation-contraction coupling • ischemia
This article has been cited by other articles:
 |
|
 |
|
  A. S. Barth and G. F. Tomaselli Cardiac Metabolism and Arrhythmias Circ Arrhythmia Electrophysiol, June 1, 2009; 2(3): 327 - 335. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kapur, J. A. Wasserstrom, J. E. Kelly, A. H. Kadish, and G. L. Aistrup Acidosis and ischemia increase cellular Ca2+ transient alternans and repolarization alternans susceptibility in the intact rat heart Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1491 - H1512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Said, R. Becerra, J. Palomeque, G. Rinaldi, M. A. Kaetzel, P. L. Diaz-Sylvester, J. A. Copello, J. R. Dedman, C. Mundina-Weilenmann, L. Vittone, et al. Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart. Role of Ca2+/calmodulin-dependent protein kinase II Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1669 - H1683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Domeier, A. V. Zima, J. T. Maxwell, S. Huke, G. A. Mignery, and L. A. Blatter IP3 receptor-dependent Ca2+ release modulates excitation-contraction coupling in rabbit ventricular myocytes Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H596 - H604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bull, J. P. Finkelstein, A. Humeres, M. I. Behrens, and C. Hidalgo Effects of ATP, Mg2+, and redox agents on the Ca2+ dependence of RyR channels from rat brain cortex Am J Physiol Cell Physiol, July 1, 2007; 293(1): C162 - C171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. E. D. J. ter Keurs and P. A. Boyden Calcium and Arrhythmogenesis Physiol Rev, April 1, 2007; 87(2): 457 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-T. Jin, N. Hasebe, T. Matsusaka, S. Natori, T. Ohta, S. Tsuji, and K. Kikuchi Magnesium attenuates isoproterenol-induced acute cardiac dysfunction and beta-adrenergic desensitization Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1593 - H1599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chugun, O. Sato, H. Takeshima, and Y. Ogawa Mg2+ activates the ryanodine receptor type 2 (RyR2) at intermediate Ca2+ concentrations Am J Physiol Cell Physiol, January 1, 2007; 292(1): C535 - C544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Shutt, G. R. Ferrier, and S. E. Howlett Increases in diastolic [Ca2+] can contribute to positive inotropy in guinea pig ventricular myocytes in the absence of changes in amplitudes of Ca2+ transients Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1623 - H1634. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Picht, J. DeSantiago, L. A. Blatter, and D. M. Bers Cardiac Alternans Do Not Rely on Diastolic Sarcoplasmic Reticulum Calcium Content Fluctuations Circ. Res., September 29, 2006; 99(7): 740 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J Crampin, N. P Smith, A. E. Langham, R. H Clayton, and C. H Orchard Acidosis in models of cardiac ventricular myocytes Phil Trans R Soc A, May 15, 2006; 364(1842): 1171 - 1186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Vornanen Temperature and Ca2+ dependence of [3H]ryanodine binding in the burbot (Lota lota L.) heart Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2006; 290(2): R345 - R351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Brunet, T. Scheuer, R. Klevit, and W. A. Catterall Modulation of CaV1.2 Channels by Mg2+ Acting at an EF-hand Motif in the COOH-terminal Domain J. Gen. Physiol., September 26, 2005; 126(4): 311 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. H. Fukumoto, S. T. Lamp, C. Motter, J. H.B. Bridge, A. Garfinkel, and J. I. Goldhaber Metabolic Inhibition Alters Subcellular Calcium Release Patterns in Rat Ventricular Myocytes: Implications for Defective Excitation-Contraction Coupling During Cardiac Ischemia and Failure Circ. Res., March 18, 2005; 96(5): 551 - 557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Eisner, M. E. Diaz, Y. Li, S. C. O'Neill, and A. W. Trafford Stability and instability of regulation of intracellular calcium Exp Physiol, January 1, 2005; 90(1): 3 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Baumgartner, H. Patel, and D. L. Barber Na+/H+ exchanger NHE1 as plasma membrane scaffold in the assembly of signaling complexes Am J Physiol Cell Physiol, October 1, 2004; 287(4): C844 - C850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kockskamper, G. U. Ahmmed, A. V. Zima, K. A. Sheehan, H. G. Glitsch, and L. A. Blatter Palytoxin disrupts cardiac excitation-contraction coupling through interactions with P-type ion pumps Am J Physiol Cell Physiol, August 1, 2004; 287(2): C527 - C538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Lehnart, X. H.T. Wehrens, P. J. Laitinen, S. R. Reiken, S.-X. Deng, Z. Cheng, D. W. Landry, K. Kontula, H. Swan, and A. R. Marks Sudden Death in Familial Polymorphic Ventricular Tachycardia Associated With Calcium Release Channel (Ryanodine Receptor) Leak Circulation, June 29, 2004; 109(25): 3208 - 3214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. H. T. Wehrens, S. E. Lehnart, S. R. Reiken, S.-X. Deng, J. A. Vest, D. Cervantes, J. Coromilas, D. W. Landry, and A. R. Marks Protection from Cardiac Arrhythmia Through Ryanodine Receptor-Stabilizing Protein Calstabin2 Science, April 9, 2004; 304(5668): 292 - 296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Zima, J. A. Copello, and L. A. Blatter Effects of cytosolic NADH/NAD+ levels on sarcoplasmic reticulum Ca2+ release in permeabilized rat ventricular myocytes J. Physiol., March 15, 2004; 555(3): 727 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zahradnikova, Z. Kubalova, J. Pavelkova, S. Gyorke, and I. Zahradnik Activation of calcium release assessed by calcium release-induced inactivation of calcium current in rat cardiac myocytes Am J Physiol Cell Physiol, February 1, 2004; 286(2): C330 - C341. [Abstract] [Full Text]
|
|
|
|
|
|
E. H. Lee, J. R. Lopez, J. Li, F. Protasi, I. N. Pessah, D. H. Kim, and P. D. Allen Conformational coupling of DHPR and RyR1 in skeletal myotubes is influenced by long-range allosterism: evidence for a negative regulatory module Am J Physiol Cell Physiol, January 1, 2004; 286(1): C179 - C189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zahradnikova, M. Dura, I. Gyorke, A. L. Escobar, I. Zahradnik, and S. Gyorke Regulation of dynamic behavior of cardiac ryanodine receptor by Mg2+ under simulated physiological conditions Am J Physiol Cell Physiol, November 1, 2003; 285(5): C1059 - C1070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Rodriguez, M. S. Bhogal, and J. Colyer Stoichiometric Phosphorylation of Cardiac Ryanodine Receptor on Serine 2809 by Calmodulin-dependent Kinase II and Protein Kinase A J. Biol. Chem., October 3, 2003; 278(40): 38593 - 38600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V Zima, J. Kockskamper, R. Mejia-Alvarez, and L. A Blatter Pyruvate Modulates Cardiac Sarcoplasmic Reticulum Ca2+ Release in Rats Via Mitochondria-Dependent and -Independent Mechanisms J. Physiol., August 1, 2003; 550(3): 765 - 783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S C O'Neill and D A Eisner pH-dependent and -independent effects inhibit Ca2+-induced Ca2+ release during metabolic blockade in rat ventricular myocytes J. Physiol., July 15, 2003; 550(2): 413 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. M. Chan, W. Welch, and R. Sitsapesan Structural Characteristics That Govern Binding to, and Modulation through, the Cardiac Ryanodine Receptor Nucleotide Binding Site Mol. Pharmacol., January 1, 2003; 63(1): 174 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E Pollard, W. E Cascio, V. G Fast, and S. B Knisley Modulation of triggered activity by uncoupling in the ischemic border: A model study with phase 1b-like conditions Cardiovasc Res, December 1, 2002; 56(3): 381 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.E. Diaz, D.A. Eisner, and S.C. O'Neill Depressed Ryanodine Receptor Activity Increases Variability and Duration of the Systolic Ca2+ Transient in Rat Ventricular Myocytes Circ. Res., October 4, 2002; 91(7): 585 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fill and J. A. Copello Ryanodine Receptor Calcium Release Channels Physiol Rev, October 1, 2002; 82(4): 893 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nomura, H. Satoh, H. Terada, M. Matsunaga, H. Watanabe, and H. Hayashi CaMKII-dependent reactivation of SR Ca2+ uptake and contractile recovery during intracellular acidosis Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H193 - H203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Matsusaka, N. Hasebe, Y.-T. Jin, J. Kawabe, and K. Kikuchi Magnesium reduces myocardial infarct size via enhancement of adenosine mechanism in rabbits Cardiovasc Res, June 1, 2002; 54(3): 568 - 575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. CROZATIER, T. BADOUAL, E. BOEHM, P.-V. ENNEZAT, T. GUENOUN, J. SU, V. VEKSLER, L. HITTINGER, and R. VENTURA-CLAPIER Role of creatine kinase in cardiac excitation-contraction coupling: studies in creatine kinase-deficient mice FASEB J, May 1, 2002; 16(7): 653 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G L Smith and S C O'Neill A comparison of the effects of ATP and tetracaine on spontaneous Ca2+ release from rat permeabilised cardiac myocytes J. Physiol., July 1, 2001; 534(1): 37 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Overend, D. A. Eisner, and S. C. O'Neill Altered Cardiac Sarcoplasmic Reticulum Function of Intact Myocytes of Rat Ventricle During Metabolic Inhibition Circ. Res., February 2, 2001; 88(2): 181 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Landeira-Fernandez Ca(2+ )transport by the sarcoplasmic reticulum Ca(2+)-ATPase in sea cucumber (Ludwigothurea grisea) muscle J. Exp. Biol., January 3, 2001; 204(5): 909 - 921. [Abstract] [PDF]
|
|
|
|
|
|
H S Choi, A W Trafford, C H Orchard, and D A Eisner The effect of acidosis on systolic Ca2+ and sarcoplasmic reticulum calcium content in isolated rat ventricular myocytes J. Physiol., December 15, 2000; 529(3): 661 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Eisner, H. S. Choi, M. E. Diaz, S. C. O'Neill, and A. W. Trafford Integrative Analysis of Calcium Cycling in Cardiac Muscle Circ. Res., December 8, 2000; 87(12): 1087 - 1094. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. G. Hampton, J.-F. Wang, J. DeAngelis, I. Amende, K. D. Philipson, and J. P. Morgan Enhanced gene expression of Na+/Ca2+ exchanger attenuates ischemic and hypoxic contractile dysfunction Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2846 - H2854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C D Balnave and R D Vaughan-Jones Effect of intracellular pH on spontaneous Ca2+ sparks in rat ventricular myocytes J. Physiol., October 1, 2000; 528(1): 25 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S Launikonis and D G. Stephenson Effects of Mg2+ on Ca2+ release from sarcoplasmic reticulum of skeletal muscle fibres from yabby (crustacean) and rat J. Physiol., July 15, 2000; 526(2): 299 - 312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yang and D. S Steele Effects of cytosolic ATP on spontaneous and triggered Ca2+-induced Ca2+ release in permeabilised rat ventricular myocytes J. Physiol., February 15, 2000; 523(1): 29 - 44. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A W Trafford, M E Diaz, G C Sibbring, and D A Eisner Modulation of CICR has no maintained effect on systolic Ca2+: simultaneous measurements of sarcoplasmic reticulum and sarcolemmal Ca2+ fluxes in rat ventricular myocytes J. Physiol., January 15, 2000; 522(2): 259 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Choisy, C. Huchet-Cadiou, and C. Léoty Sarcoplasmic Reticulum Ca2+ Release by 4-Chloro-m-Cresol (4-CmC) in Intact and Chemically Skinned Ferret Cardiac Ventricular Fibers J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 578 - 586. [Abstract] [Full Text]
|
|
|
|
|
|
E. Carmeliet Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias Physiol Rev, July 1, 1999; 79(3): 917 - 1017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Petrecca, R. Atanasiu, S. Grinstein, J. Orlowski, and A. Shrier Subcellular localization of the Na+/H+ exchanger NHE1 in rat myocardium Am J Physiol Heart Circ Physiol, February 1, 1999; 276(2): H709 - H717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J Lokuta, A. Darszon, C. Beltran, and H. H Valdivia Detection and functional characterization of ryanodine receptors from sea urchin eggs J. Physiol., July 1, 1998; 510(1): 155 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.A Eisner, A.W Trafford, M.E Dnaz, C.L Overend, and S.C O'Neill The control of Ca release from the cardiac sarcoplasmic reticulum: regulation versus autoregulation Cardiovasc Res, June 1, 1998; 38(3): 589 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Xu, J. P. Eu, G. Meissner, and J. S. Stamler Activation of the Cardiac Calcium Release Channel (Ryanodine Receptor) by Poly-S-Nitrosylation Science, January 9, 1998; 279(5348): 234 - 237. [Abstract] [Full Text]
|
|
|
|
|
|
W. Liu, D. A. Pasek, and G. Meissner Modulation of Ca2+-gated cardiac muscle Ca2+-release channel (ryanodine receptor) by mono- and divalent ions Am J Physiol Cell Physiol, January 1, 1998; 274(1): C120 - C128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yang and D. S. Steele Effects of Cytosolic ATP on Ca2+ Sparks and SR Ca2+ Content in Permeabilized Cardiac Myocytes Circ. Res., September 14, 2001; 89(6): 526 - 533. [Abstract] [Full Text] [PDF]
|
|