Changes in intracellular Ca²⁺ are required for contraction of cardiac myocytes. To meet the increased hameodynamic requirements associated with exercise or stress, cardiac output is enhanced through an increase in the frequency and force of contraction of cardiomyocytes. As a result of a prolonged increased in workload the heart undergoes hypertrophy. This adaptive response is manifest as an enlargement of the heart ventricles that is due to an increase in cell size without an increase in cell number. Interestingly, as well as controlling cardiomyocyte contraction, Ca²⁺ also plays a key role in regulating the transcription of genes involved in the hypertrophic response. Several models have been proposed to explain how Ca²⁺ can simultaneously, and with great fidelity, specifically control transcription and contraction in cardiac myocytes. Contraction and transcription are regulated in a linear fashion by the frequency and/or amplitude of Ca²⁺ transients. Alternatively, contraction and transcription are controlled by Ca²⁺ elevations that are either temporally or spatially distinct. Recently, inositol 1,4,5-trisphosphate receptor (InsP3Rs) intracellular Ca²⁺ release channels have been shown to be expressed and functional in adult cardiac myocytes. InsP3Rs are expressed at approximately 100-fold lower level than ryanodine receptors (RyRs), which are responsible for mediating the Ca²⁺ release required to induce contraction. InsP3Rs also exhibit a restricted distribution in cardiac myocytes and unlike RyRs, which are located throughout the sarcoplasmic reticulum, they exhibit a sub-plasmalemmal and perinuclear distribution (1). This raises the possibility that they could give rise to Ca²⁺ signals that are distinct from those arising through RyRs. Recent evidence indicates that Ca²⁺ release through InsP3Rs occurs in response to cellular stimulation with endothelin-1 (ET-1). ET-1 is a well-known vasoactive hormone and a potent pro-hypertrophic agonist. The dual roles of ET-1 and InsP3-induced Ca²⁺ release in myocyte contraction and hypertrophy will be discussed.