Calcium biology of the transverse tubules in heart.
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).
Song
Long-Sheng
LS
Medical Biotechnology Center and the Institute of Molecular Cardiology, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201, USA.
Guatimosim
Silvia
S
Gómez-Viquez
Leticia
L
Sobie
Eric A
EA
Ziman
Andrew
A
Hartmann
Hali
H
Lederer
W J
WJ
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D004594:Electrophysiology; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D012518:Sarcomeres / Q000502:physiology* / Q000648:ultrastructure; D012519:Sarcoplasmic Reticulum / Q000502:physiology* / Q000648:ultrastructure
D019837:Ryanodine Receptor Calcium Release Channel