t-tubules and sarcoplasmic reticulum function in cardiac ventricular myocytes

Although the existence of t-tubules in mammalian cardiac ventricular myocytes has been recognized 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 (SR), thereby allowing rapid and synchronous Ca2+ release throughout the cell; I Ca 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 SR 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 SR, 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. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007.