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 duBell, W H Articles by Rogers, T B Search for Related Content PubMed PubMed Citation Articles by duBell, W H Articles by Rogers, T B

Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore 21201, USA.

1. We examined the effects of the immunosupressant drug FK506 on excitation-contraction coupling in isolated rat ventricular myocytes. [Ca2+]i transients were recorded using the intracellular Ca2+ indicators fluo-3 and indo-1 while action potentials (APs) or membrane currents were recorded using patch-type microelectrodes in the whole cell mode. 2. FK506 (25 microM) rapidly and reversibly increased the magnitude of the [Ca2+]i transient in intact cells without changing resting [Ca2+]i or the kinetics of the [Ca2+]i transient, a finding consistent with previous reports that investigated the actions of FK506 on the sarcoplasmic reticulum Ca2+ release channel. 3. The 36% increase in the [Ca2+]i transient produced by FK506 was accompanied by a 293% increase in AP duration (by 293%). Importantly, the addition of FK506 had no effect on the [Ca2+]i transient when the depolarizing duration was controlled in voltage clamp experiments. The increased AP duration could be explained by a marked inward shift in the net membrane current that was observed in these experiments. 4. The net inward current change was not directly responsible for a change in Ca2+ influx, since no change in L-type Ca2+ current (ICa) was observed. Instead, FK506 inhibited both the transient outward K+ current (Ito) and the delayed rectifier K+ current (IK). 5. We conclude that FK506 increases the [Ca2+]i transient during normal contractions by an indirect action: it prolongs the action potential. This action does not appear to depend on the established action of FK506 on the ryanodine receptor. Instead, the inhibition of outward K+ currents prolongs the AP which secondarily increases Ca2+ influx and/or decreases Ca2+ efflux.

This article has been cited by other articles:

				N. Bhasin, S. R. Cunha, M. Mudannayake, M. S. Gigena, T. B. Rogers, and P. J. Mohler Molecular basis for PP2A regulatory subunit B56{alpha} targeting in cardiomyocytes Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H109 - H119. [Abstract] [Full Text] [PDF]

				H. S. Ahn, S. E. Kim, B. H. Choi, J.-S. Choi, M.-J. Kim, D.-J. Rhie, S. H. Yoon, Y.-H. Jo, M.-S. Kim, K.-W. Sung, et al. Calcineurin-independent inhibition of KV1.3 by FK-506 (tacrolimus): a novel pharmacological property Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1714 - C1722. [Abstract] [Full Text] [PDF]

				M. S. Gigena, A. Ito, H. Nojima, and T. B. Rogers A B56 regulatory subunit of protein phosphatase 2A localizes to nuclear speckles in cardiomyocytes Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H285 - H294. [Abstract] [Full Text] [PDF]

				Y.-X. Wang, Y.-M. Zheng, Q.-B. Mei, Q.-S. Wang, M. L. Collier, S. Fleischer, H.-B. Xin, and M. I. Kotlikoff FKBP12.6 and cADPR regulation of Ca2+ release in smooth muscle cells Am J Physiol Cell Physiol, March 1, 2004; 286(3): C538 - C546. [Abstract] [Full Text]

				M. Fill and J. A. Copello Ryanodine Receptor Calcium Release Channels Physiol Rev, October 1, 2002; 82(4): 893 - 922. [Abstract] [Full Text] [PDF]

				E. A. Sobie, K. W. Dilly, J. dos Santos Cruz, W. J. Lederer, and M. S. Jafri Termination of Cardiac Ca2+ Sparks: An Investigative Mathematical Model of Calcium-Induced Calcium Release Biophys. J., July 1, 2002; 83(1): 59 - 78. [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]