Calcium Biology of the Transverse Tubules in Heart

SONG, LONG-SHENG
GUATIMOSIM, SILVIA
GÓMEZ-VIQUEZ, LETICIA
SOBIE, ERIC A.
ZIMAN, ANDREW
HARTMANN, HALI
LEDERER, W J

^aMedical Biotechnology Center and the Institute of Molecular Cardiology, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201, USA
^bDepartment of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil
^cDepartment of Pediatrics, New York University School of Medicine, New York, New York 10016, USA
^dDepartment of Physiology, University of Maryland, Baltimore, Maryland 21201, USA

Address for correspondence: Prof. W.J. Lederer, M.D., Ph.D., Medical Biotechnology Center, UMBI, 725 W. Lombard Street, Baltimore, MD 21201, USA. Voice: 410-706-8181; fax: 410-510-1545. [email protected]

Ann. N.Y. Acad. Sci. 1047: 99-111 (2005).

doi: 10.1196/annals.1341.009

Annals of the New York Academy of Sciences 1047:p 99-111, 2005.

Ca²⁺ sparks in heart muscle are activated on depolarization by the influx of Ca²⁺ through dihydropyridine receptors in the sarcolemmal (SL) and transverse tubule (TT) membranes. The cardiac action potential is thus able to synchronize the [Ca²⁺]_i transient as Ca²⁺ release is activated throughout the cell. Increases in the amount of Ca²⁺ within the sarcoplasmic reticulum (SR) underlie augmented Ca²⁺ release globally and an increase in the sensitivity of the ryanodine receptors (RyRs) to be triggered by the local [Ca²⁺]_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 [Ca²⁺]_i. Heart failure and other cardiac diseases are associated with changes in SR Ca²⁺ content, phosphorylation state of the RyRs, [Ca²⁺]_i signaling defects and arrhythmias. Additional changes in transverse tubules and nearby junctional SR may contribute to alterations in local Ca²⁺ signaling. Here we briefly discuss how TT organization can influence Ca²⁺ signaling and how changes in SR Ca²⁺ 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 Ca²⁺ signaling may be regulated in health and disease. Three issues are examined in this presentation: (1) normal Ca²⁺-induced Ca²⁺ release and Ca²⁺ sparks, (2) abnormal SR Ca²⁺ release in disease, and (3) the triggering and propagation of waves of elevated [Ca²⁺]_i.