alcium ion (Ca 2+ ) is a major intracellular messenger with a vital role in many cellular responses. In cardiac myocytes, Ca 2+ not only transmits an electrical signal to the sarcomere thereby triggering a mechanical event, but also induces the expression of genes responsible for hypertrophy or apoptosis. Signaling via Ca 2+ occurs through transient changes in the intracellular Ca 2+ concentration ([Ca 2+ ]i), which is maintained between 10 nmol/L and 10 μmol/L with physiological Ca 2+ transients occurring within this range. The diversity of Ca 2+ -mediated effects is attributable to differences in the amplitude and spatiotemporal pattern of Ca 2+ transients. 1 In cardiac myocytes, intracellular Ca 2+ has 2 origins: the extracellular space and the sarcoplasmic reticulum (SR). The roles of the SR and ryanodine receptors in heart disease have been described by Yano. 2 Here, we focus here on the involvement of Ca 2+ -entry channels in the development of heart disease.The extracellular milieu is a ready source of Ca 2+ , and several ion channels allow Ca 2+ to enter the cell. In cardiac myocytes, voltage-gated Ca 2+ channels (VGCC) mediate Ca 2+ entry upon depolarization of the cell membrane above a threshold potential during an action potential. Ca 2+ entry is mediated partly by the Na + /Ca 2+ exchanger (NCX) running in 'reverse mode'. Other Ca 2+ -entry pathways include ligandgated cation channels (LGC), stretch-activated cation channels (SAC), thermosensitive channels, and receptor-activated cation channels (RAC).LGC are gated by the binding of a ligand to the channel itself. SAC and thermosensitive channels are activated by mechanical stretching and changes in the ambient temperature, respectively. RAC are gated by agonist binding to a receptor distinct from the channel protein. RAC subtypes exist with different Ca 2+ selectivities, activation mechanisms, and physiological functions; these include store-operated Ca 2+ channels (SOC), which are activated upon depletion of the intracellular Ca 2+ store, and receptor-operated Ca 2+ channels (ROC), which are activated by diacylglycerol (DAG).With the exceptions of VGCC and NCX, the molecular identities of Ca 2+ -entry channels have not yet been completely determined, although new findings have emerged in recent years. Novel players regulating Ca 2+ entry have been found in the still-growing family of transient receptor potential (TRP) cation channels. The identification of mammalian TRP channels was a new starting point in the search for the molecular identification of Ca 2+ -entry pathways that contribute to the development of heart disease. This review discusses the expression and function of TRP channels in the heart, their endogenous agonists, the pathophysiological conditions that can modulate these channels, and the potential involvement of TRP channels in the pathogenesis of certain heart diseases such as cardiac hypertrophy, muscular dystrophy associated cardiomyopathy and arrhythmias under Ca 2+ -overload conditions.
TRP SuperfamilyDrosophila with mutatio...