Article,

Differential modulation of L-type Ca$^2+$ current by SR Ca$^2+$ release at the T-tubules and surface membrane of rat ventricular myocytes.

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Circ. Res., 95 (1): e1--e7 (July 2004)
DOI: 10.1161/01.RES.0000135547.53927.F6

Abstract

We have characterized modulation of ICa by Ca$^2+$ 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 Ca$^2+$ 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 Ca$^2+$ release from the SR, because the gain of Ca$^2+$ release was not significantly different in control and detubulated cells. These data suggest that the t-tubules are a key site for the regulation of transsarcolemmal Ca$^2+$ flux by Ca$^2+$ release from the SR; this could play a role in altered Ca$^2+$ homeostasis in pathological conditions. The full text of this article is available online at http://circres.ahajournals.org.

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