Differential modulation of L-type Ca2+ current by SR Ca2+ release at the T-tubules and surface membrane of rat ventricular myocytes.
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 not significantly different 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.
Brette
Fabien
F
School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK. f.brette@leeds.ac.uk
Sallé
Laurent
L
Orchard
Clive H
CH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D004553:Electric Conductivity; D006352:Heart Ventricles / Q000166:cytology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D020746:Calcium Channels, L-Type; D002118:Calcium