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 Ca(2+) current (I(Ca)) flowing across the t-tubule membrane provides a rapidly inactivating Ca(2+) influx that triggers Ca(2+) release from the sarcoplasmic reticulum (SR), thereby allowing rapid and synchronous Ca(2+) 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 Ca(2+). In contrast, although its density is lower, I(Ca) flowing across the surface membrane inactivates slowly, and thus may help load the SR with Ca(2+). There is also increasing evidence that many of the mechanisms that remove Ca(2+) from the cytoplasm are located predominantly at the t-tubules, which therefore play an important role in determining cellular, and hence SR, Ca(2+) content. Thus, the t-tubules appear to play a central role in the increase and subsequent decrease of Ca(2+) during the systolic Ca(2+) 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.