Differential Modulation of L-type Ca 2+ Current by SR Ca 2+ Release at the T-Tubules and Surface Membrane of Rat Ventricular Myocytes

Abstract

We have characterized modulation of I Ca 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 I Ca . I Ca 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, I Ca inactivation was not changed by the treatment used to produce detubulation. In the presence of ryanodine or BAPTA, or when Ba 2+ 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 I Ca 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.