Cardiovascular Research Advance Access [Accepted Manuscript] published online on August 14, 2007
Cardiovascular Research, doi:10.1093/cvr/cvm002
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T-TUBULES AND SARCOPLASMIC RETICULUM FUNCTION IN CARDIAC VENTRICULAR MYOCYTES
1 Department of Physiology, University of Bristol, Bristol, BS8 1TD, U.K.
2 Faculty of Life Sciences, University of Manchester, Manchester, M13 9NT, U.K.
Correspondence to: Clive Orchard, Department of Physiology, University of Bristol, Bristol BS8 1TD, UK e-mail: clive.orchard{at}bristol.ac.uk. Tel & FAX: +44-(0)117-331-7289
Although the existence of t-tubules in mammalian cardiac ventricular myocytes has been recognised for a long time, it now appears that their structure and function are more complex than previously believed. Recent work has provided evidence that many of the key proteins underlying excitation-contraction coupling are located predominantly at the t-tubules. L-type Ca2+ current (ICa) flowing across the t-tubule membrane provides a rapidly inactivating Ca2+ influx that triggers Ca2+ release from the sarcoplasmic reticulum, thereby allowing rapid and synchronous Ca2+ release throughout the cell; ICa at the t-tubules also appears to be more sensitive than that at the surface membrane to regulation by beta-adrenergic stimulation and intracellular Ca2+. In contrast, although its density is lower, ICa flowing across the surface membrane inactivates slowly, and thus may help load the sarcoplasmic reticulum with Ca2+. There is also increasing evidence that many of the mechanisms that remove Ca2+ from the cytoplasm are located predominantly at the t-tubules, which therefore play an important role in determining cellular, and hence sarcoplasmic reticulum, Ca2+ content. Thus the t-tubules appear to play a central role in the increase and subsequent decrease of Ca2+ during the systolic Ca2+ transient. Remodelling of the t-tubules has been reported in cardiac pathologies, and may play a role in the altered cellular, and hence cardiac, function observed in such conditions.
KEYWORDS cardiac muscle; t-tubules; calcium; excitation-contraction coupling; sarcoplasmic reticulum; heart failure
Time for primary review: 23 days
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