Calcium Biology of the Transverse Tubules in Heart

A bstract : Ca 2+ sparks in heart muscle are activated on depolarization by the influx of Ca 2+ through dihydropyridine receptors in the sarcolemmal (SL) and transverse tubule (TT) membranes. The cardiac action potential is thus able to synchronize the [Ca 2+ ] i transient as Ca 2+ release is activated throughout the cell. Increases in the amount of Ca 2+ within the sarcoplasmic reticulum (SR) underlie augmented Ca 2+ release globally and an increase in the sensitivity of the ryanodine receptors (RyRs) to be triggered by the local [Ca 2+ ] i . In a similar manner, phosphorylation of the RyRs by protein kinase A (PKA) increases the sensitivity of the RyRs to be activated by local [Ca 2+ ] i . Heart failure and other cardiac diseases are associated with changes in SR Ca 2+ content, phosphorylation state of the RyRs, [Ca 2+ ] i signaling defects and arrhythmias. Additional changes in transverse tubules and nearby junctional SR may contribute to alterations in local Ca 2+ signaling. Here we briefly discuss how TT organization can influence Ca 2+ signaling and how changes in SR Ca 2+ release triggering can influence excitation‐contraction (EC) coupling. High speed imaging methods are used in combination with single cell patch clamp experiments to investigate how abnormal Ca 2+ signaling may be regulated in health and disease. Three issues are examined in this presentation: (1) normal Ca 2+ ‐induced Ca 2+ release and Ca 2+ sparks, (2) abnormal SR Ca 2+ release in disease, and (3) the triggering and propagation of waves of elevated [Ca 2+ ] i .