The role of inositol 1,4,5‐trisphosphate receptors in Ca²⁺ signalling and the generation of arrhythmias in rat atrial myocytes

Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes

“…So, with substantial increases of intracellular IP 3 concentrations as may occur following stimulation of cardiomyocytes with G q protein-coupled agonists, IP 3 Rs can become activated at normal diastolic Ca 2+ levels, or during the recovery of a stimulated Ca 2+ transient [62]. The promiscuous opening of IP 3 Rs during the otherwise quiescent diastolic period under these conditions is therefore the cause of arrhythmic Ca 2+ transients and their associated electrical activity [63,64].…”

“…As outlined below, exposure of cardiac myocytes to G q protein-coupled agonists or membrane-permeable analogues of IP 3 causes a sustained increase in global Ca 2+ transients, e.g. [63,[70][71][72], with SR Ca 2+ load staying unchanged or even tending to decrease [72]. Thus, IP 3 uniquely alters cardiac excitation-contraction coupling in that it increases Ca 2+ transients and fractional SR Ca 2+ release at largely unaltered SR Ca 2+ load.…”

The cardiac IP3 receptor: Uncovering the role of “the other” calcium-release channel

“…However, there is great and growing interest in cardiac IP 3 signaling due to the known importance of several IP 3 -inducing agonists (e.g. angiotensin II, endothelin, and norepinephrine) in hypertrophy and heart failure [7][8][9][10][11][12][13][14][15].While agonist-induced IP 3 -dependent Ca 2+ release is readily observed in most tissues, the role of IP 3 Rs in cardiac tissue is less clear. The subcellular localization of IP 3 Rs in cardiac myocytes has received increasing attention as the field attempts to define the function of these channels.…”

“…However, there is great and growing interest in cardiac IP 3 signaling due to the known importance of several IP 3 -inducing agonists (e.g. angiotensin II, endothelin, and norepinephrine) in hypertrophy and heart failure [7][8][9][10][11][12][13][14][15].…”

“…In ventricular myocytes, immunofluorescence studies show that IP 3 Rs are found at the Z-lines, in the perinuclear region and in the nuclear membrane [7,16,17]. Moreover, IP 3 Rs are found in similar locations in both atrial [12] and Purkinje myocytes [18][19][20]). The role(s) played by these IP 3 Rs have yet to be convincingly demonstrated, but provocative suggestions for their function include modulation of transcription [21], amplification of RyR2 Ca 2+ signals [9], and independent activation through diverse pathways that generate IP 3 [22,23].…”