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Circulation Research. 2004
Published online before print June 10, 2004, doi: 10.1161/01.RES.0000135547.53927.F6
A more recent version of this article appeared on July 9, 2004
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Right arrow Calcium cycling/excitation-contraction coupling
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Submitted on July 1, 2003
Revised on May 28, 2004
Accepted on June 3, 2004

Differential Modulation of L-type Ca2+ Current by SR Ca2+ Release at the T-Tubules and Surface Membrane of Rat Ventricular Myocytes

F. Brette *; L. Sallé ; and C. H. Orchard

From the School of Biomedical Sciences (F.B., C.H.O.), University of Leeds, Leeds, UK; and the Laboratoire de Physiologie Cellulaire (L.S.), Université de Caen, Caen, France.

* To whom correspondence should be addressed. E-mail: f.brette{at}leeds.ac.uk.

We have characterized modulation of ICa by Ca2+ at the t-tubules (ie, in control cells) and surface sarcolemma (ie, in detubulated cells) of cardiac ventricular myocytes, using the whole-cell patch clamp technique to record ICa. ICa inactivation was significantly slower in detubulated cells than in control cells (27.1±7.8 ms, n=22, versus 16.4±7.9 ms, n=22; P<0.05). In atrial myocytes, which lack t-tubules, ICa inactivation was not changed by the treatment used to produce detubulation. In the presence of ryanodine or BAPTA, or when Ba2+ was used as the charge carrier, the rate of inactivation was not significantly different in control and detubulated cells. Frequency-dependent facilitation occurred in control cells but not in detubulated cells, and was abolished by ryanodine. These results suggest that Ca2+ released from the SR has a greater effect on ICa in the t-tubules than at the surface sarcolemma. This does not appear to be due to differences in local Ca2+ release from the SR, because the gain of Ca2+ release was the same in control and detubulated cells. These data suggest that the t-tubules are a key site for the regulation of transsarcolemmal Ca2+ flux by Ca2+ release from the SR; this could play a role in altered Ca2+ homeostasis in pathological conditions. The full text of this article is available online at http://circres.ahajournals.org.


Key words: transverse tubules • calcium channel • inactivation • facilitation.




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