HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yang, Z. Articles by Steele, D. S. Search for Related Content PubMed PubMed Citation Articles by Yang, Z. Articles by Steele, D. S.

Effects of cytosolic ATP on spontaneous and triggered Ca²⁺-induced Ca²⁺ release in permeabilised rat ventricular myocytes

Zhaokang Yang and Derek S. Steele

1. The effects of cytosolic ATP on sarcoplasmic reticulum (SR) Ca²⁺ regulation were investigated in saponin-permeabilised rat ventricular myocytes. [Ca²⁺] within the cells was monitored using Fura-2 or Fluo-3 fluorescence. Spontaneous cyclic Ca²⁺ release from the SR was induced by increasing the bathing [Ca²⁺] to 200-300 nM, in solutions weakly Ca²⁺ buffered with 0·05 mM EGTA. Alternatively, Ca²⁺-induced Ca²⁺ release (CICR) was triggered by a rapid increase in [Ca²⁺] induced by flash photolysis of Nitr-5 (0·08 mM), replacing EGTA in the solution.

2. Stepwise reductions in [ATP] were associated with corresponding decreases in the frequency and increases in the amplitude of spontaneous Ca²⁺ transients. A decrease from 5 mM to 0·1 mM ATP, reduced the release frequency by 48·6 ± 7 % (n = 7) and almost doubled the amplitude of the Ca²⁺ transient. Marked prolongation of the spontaneous Ca²⁺ transient occurred when [ATP] was further reduced to 10 µM, consistent with inhibition of the SR Ca²⁺ pump.

3. These effects of ATP were compared with other interventions that inhibit Ca²⁺ uptake or reduce the sensitivity of the SR Ca²⁺ release mechanism. Inhibition of the SR Ca²⁺ pump with cyclopiazonic acid (CPA) markedly reduced the spontaneous Ca²⁺ release frequency, without changing the amplitude. The descending phase of the Ca²⁺ transient was prolonged in the presence of CPA, while the rising phase was unaffected. In contrast, desensitisation of the SR Ca²⁺ release mechanism with tetracaine decreased the frequency of spontaneous release, but markedly increased the amplitude.

4. CICR triggered by flash photolysis of Nitr-5 appeared to be more sensitive to cytosolic [ATP] than spontaneous release and was generally delayed by a decrease to 2·5 mM ATP. In the presence of 0·1-0·2 mM ATP, release often failed completely or was not consistently triggered. Some preparations exhibited Ca²⁺ release 'alternans', whereby every alternate trigger induced a response.

5. These results suggest that the increase in spontaneous Ca²⁺ release amplitude and the decrease in frequency that occurs as [ATP] is reduced from 1 mM to 100 µM, is mainly due to desensitisation of the SR Ca²⁺ release mechanism, which allows the SR Ca²⁺ content to reach a higher level before release occurs. At very low [ATP], a reduction in the SR Ca²⁺ uptake rate may also contribute to the decrease in release frequency. CICR triggered by photolysis of Nitr-5 appeared to be more sensitive to cytosolic [ATP]. The possible underlying mechanisms and the relevance of these results to myocardial ischaemia or hypoxia is considered.

This article has been cited by other articles:

				Z. Yang, N. Ikemoto, G. D. Lamb, and D. S. Steele The RyR2 central domain peptide DPc10 lowers the threshold for spontaneous Ca2+ release in permeabilized cardiomyocytes Cardiovasc Res, June 1, 2006; 70(3): 475 - 485. [Abstract] [Full Text] [PDF]

				D. Meng, L. Feng, X.-J. Chen, D. Yang, and J.-N. Zhang Trimetazidine improved Ca2+ handling in isoprenalinemediated myocardial injury of rats Exp Physiol, May 1, 2006; 91(3): 591 - 601. [Abstract] [Full Text] [PDF]

				H. A. Shiels and E. White Temporal and spatial properties of cellular Ca2+ flux in trout ventricular myocytes Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1756 - R1766. [Abstract] [Full Text] [PDF]

				Z. Yang and D. S. Steele Characteristics of Prolonged Ca2+ Release Events Associated With the Nuclei in Adult Cardiac Myocytes Circ. Res., January 7, 2005; 96(1): 82 - 90. [Abstract] [Full Text] [PDF]

				Z. Yang, S. M. Harrison, and D. S. Steele ATP-dependent effects of halothane on SR Ca2+ regulation in permeabilized atrial myocytes Cardiovasc Res, January 1, 2005; 65(1): 167 - 176. [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]

				R. Dumollard, K. Hammar, M. Porterfield, P. J. Smith, C. Cibert, C. Rouviere, and C. Sardet Mitochondrial respiration and Ca2+ waves are linked during fertilization and meiosis completion Development, February 15, 2003; 130(4): 683 - 692. [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]

				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]

				Z. Yang and D. S. Steele Effects of phosphocreatine on SR Ca2+ regulation in isolated saponin-permeabilized rat cardiac myocytes J. Physiol., March 15, 2002; 539(3): 767 - 777. [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]