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

This Article 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 O'Neill, S C Articles by Eisner, D A Search for Related Content PubMed PubMed Citation Articles by O'Neill, S C Articles by Eisner, D A

Department of Physiology, University College London.

1. The fluorescent indicator Indo-1 was used to measure both [Ca2+]i and [caffeine]i in single ventricular myocytes. 2. Caffeine (at concentrations of 1 mM or above) produced a transient increase of resting [Ca2+]i attributed to the release of Ca2+ ions from the sarcoplasmic reticulum (SR). Simultaneous measurement of [caffeine]i showed that the Ca2+ release only began when [caffeine]i had risen to about 1 mM. Subsequently the rate of release was a steep function of [caffeine]i. It is suggested that this results from a positive feedback as the Ca2+ released activates further release. 3. If external Ca2+ was removed the release of Ca2+ produced by caffeine was delayed such that [caffeine]i rose to a greater concentration before release was initiated. This suggests that an increase of [Ca2+]i increases the efficacy of caffeine to release Ca2+ ions from the SR. 4. Lower concentrations of caffeine (50-500 microM) had no effect on diastolic [Ca2+]i. In contrast they increased systolic [Ca2+]i and contraction. This increase was most obvious if the systolic contraction had previously been decreased either by reducing [Ca2+]o from 1 to 0.25 mM or (in voltage-clamped cells) by decreasing the magnitude of the depolarizing pulse. 5. If the exposure to caffeine was prolonged, this increase of systolic [Ca2+]i and contraction was completely transient. On removal of caffeine, systolic [Ca2+]i and contraction decreased to below control before recovering. 6. During these transient changes of systolic [Ca2+]i and contraction there was no change of the sarcolemmal Ca2+ current. 7. It is suggested that the increase of systolic [Ca2+]i is due to caffeine increasing the fraction of the SR Ca2+ content released during the twitch. 8. The above results concerning both diastolic and systolic [Ca2+]i can be explained by a model in which caffeine increases the affinity with which Ca2+ ions activate Ca2(+)-induced Ca2+ release. At high enough [caffeine], the threshold [Ca2+]i for regenerative Ca2(+)-induced Ca2+ release will be reduced to below the resting [Ca2+]i thus producing a diastolic increase of [Ca2+]i. At lower [caffeine] the threshold is higher than resting [Ca2+]i and caffeine only serves to enhance the release produced during systole.

This article has been cited by other articles:

				P. Swietach, K. W. Spitzer, and R. D. Vaughan-Jones Ca2+-Mobility in the Sarcoplasmic Reticulum of Ventricular Myocytes Is Low Biophys. J., August 1, 2008; 95(3): 1412 - 1427. [Abstract] [Full Text] [PDF]

				G. Lim, L. Venetucci, D. A. Eisner, and B. Casadei Does nitric oxide modulate cardiac ryanodine receptor function? Implications for excitation-contraction coupling Cardiovasc Res, January 15, 2008; 77(2): 256 - 264. [Abstract] [Full Text] [PDF]

				N. Szentandrassy, M. R. Perez-Bido, E. Alonzo, N. Negretti, and S. C. O'Neill Protein kinase A is activated by the n-3 polyunsaturated fatty acid eicosapentaenoic acid in rat ventricular muscle J. Physiol., July 1, 2007; 582(1): 349 - 358. [Abstract] [Full Text] [PDF]

				L. A. VENETUCCI, A. W. TRAFFORD, S. C. O'NEILL, and D. A. EISNER Na/Ca Exchange: Regulator of Intracellular Calcium and Source of Arrhythmias in the Heart Ann. N.Y. Acad. Sci., March 1, 2007; 1099(1): 315 - 325. [Abstract] [Full Text] [PDF]

				N. BRACKEN, F. C HOWARTH, and J. SINGH Effects of Streptozotocin-Induced Diabetes on Contraction and Calcium Transport in Rat Ventricular Cardiomyocytes Ann. N.Y. Acad. Sci., November 1, 2006; 1084(1): 208 - 222. [Abstract] [Full Text] [PDF]

				S. Magne, D. Couchie, F. Pecker, and C. Pavoine beta 2-Adrenergic Receptor Agonists Increase Intracellular Free Ca2+ Concentration Cycling in Ventricular Cardiomyocytes through p38 and p42/44 MAPK-mediated Cytosolic Phospholipase A2 Activation J. Biol. Chem., October 19, 2001; 276(43): 39539 - 39548. [Abstract] [Full Text] [PDF]

				J. Prestle, P. M.L. Janssen, A. P. Janssen, O. Zeitz, S. E. Lehnart, L. Bruce, G. L. Smith, and G. Hasenfuss Overexpression of FK506-Binding Protein FKBP12.6 in Cardiomyocytes Reduces Ryanodine Receptor-Mediated Ca2+ Leak From the Sarcoplasmic Reticulum and Increases Contractility Circ. Res., February 2, 2001; 88(2): 188 - 194. [Abstract] [Full Text] [PDF]

				A. W. Trafford, M. E. Diaz, and D. A. Eisner Coordinated Control of Cell Ca2+ Loading and Triggered Release From the Sarcoplasmic Reticulum Underlies the Rapid Inotropic Response to Increased L-Type Ca2+ Current Circ. Res., February 2, 2001; 88(2): 195 - 201. [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. J. Hawke, D. G. Allen, and M. I. Lindinger Paraxanthine, a caffeine metabolite, dose dependently increases [Ca2+]i in skeletal muscle J Appl Physiol, December 1, 2000; 89(6): 2312 - 2317. [Abstract] [Full Text] [PDF]

				M.E. Diaz, A.W. Trafford, S.C. O'Neill, and D.A. Eisner Can changes of ryanodine receptor expression affect cardiac contractility? Cardiovasc Res, March 1, 2000; 45(4): 1068 - 1069. [Full Text] [PDF]

				M. Ritter, Z. Su, K. W. Spitzer, H. Ishida, and W. H. Barry Caffeine-induced Ca2+ sparks in mouse ventricular myocytes Am J Physiol Heart Circ Physiol, February 1, 2000; 278(2): H666 - H669. [Abstract] [Full Text] [PDF]

				T. Saeki, J.-B. Shen, and A. J. Pappano Inositol-1,4,5-trisphosphate increases contractions but not L-type calcium current in guinea pig ventricular myocytes Cardiovasc Res, March 1, 1999; 41(3): 620 - 628. [Abstract] [Full Text] [PDF]

				A.W. TRAFFORD, M.E. DIAZ, and D.A. EISNER Measurement of Sarcoplasmic Reticulum Ca Content and Sarcolemmal Fluxes during the Transient Stimulation of the Systolic Ca Transient Produced by Caffeine Ann. N.Y. Acad. Sci., September 16, 1998; 853(1): 368 - 371. [Full Text] [PDF]

				J. T. Hulme and C. H. Orchard Effect of acidosis on Ca2+ uptake and release by sarcoplasmic reticulum of intact rat ventricular myocytes Am J Physiol Heart Circ Physiol, September 1, 1998; 275(3): H977 - H987. [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]

				A.W Trafford, M.E Dieaz, and D.A Eisner Stimulation of Ca-induced Ca release only transiently increases the systolic Ca transient: measurements of Ca fluxes and sarcoplasmic reticulum Ca Cardiovasc Res, March 1, 1998; 37(3): 710 - 717. [Abstract] [Full Text] [PDF]

				X. Guo, M. A. Laflamme, and P. L. Becker Cyclic ADP-Ribose Does Not Regulate Sarcoplasmic Reticulum Ca2+ Release in Intact Cardiac Myocytes Circ. Res., July 1, 1996; 79(1): 147 - 151. [Abstract] [Full Text]

				A. Sauvadet, T. Rohn, F. Pecker, and C. Pavoine Synergistic Actions of Glucagon and Miniglucagon on Ca2+ Mobilization in Cardiac Cells Circ. Res., January 1, 1996; 78(1): 102 - 109. [Abstract] [Full Text]