Published online before print July 18, 2002, doi: 10.1161/01.RES.0000030180.06028.23
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Submitted on February 6, 2002
Revised on July 8, 2002
Accepted on July 8, 2002
Na+/Ca2+ Exchange Activity Is Localized in the T-Tubules of Rat Ventricular Myocytes
Z. Yang ;
From the School of Biomedical Sciences, University of Leeds, Leeds, UK.
* To whom correspondence should be addressed. E-mail: c.h.orchard{at}leeds.ac.uk.
Detubulation of rat ventricular myocytes has been used to investigate the role of the t-tubules in Ca2+ cycling during excitation-contraction coupling in rat ventricular myocytes. Ca2+ was monitored using fluo-3 and confocal microscopy. In control myocytes, electrical stimulation caused a spatially uniform increase in intracellular [Ca2+] across the cell width. After detubulation, [Ca2+] rose initially at the cell periphery and then propagated into the center of the cell. Application of caffeine to control myocytes resulted in a rapid and uniform increase of intracellular [Ca2+]; the distribution and amplitude of this increase was the same in detubulated myocytes, although its decline was slower. On application of caffeine to control cells, there was a large, rapid, and transient rise in extracellular [Ca2+] as Ca2+ was extruded from the cell; this rise was significantly smaller in detubulated cells, and the remaining increase was blocked by the sarcolemmal Ca2+ ATPase inhibitor carboxyeosin. The treatment used to produce detubulation had no significant effect on Ca2+ efflux in atrial cells, which lack t-tubules. Detubulation of ventricular myocytes also resulted in loss of Na+/Ca2+ exchange current, although the density of the fast Na+ current was unaltered. It is concluded that Na+/Ca2+ exchange function, and hence Ca2+ efflux by this mechanism, is concentrated in the t-tubules, and that the concentration of Ca2+ flux pathways in the t-tubules is important in producing a uniform increase in intracellular Ca2+ on stimulation.
Key words: t-tubules • calcium • sodium/calcium exchanger
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