The effect of ischaemia-reperfusion on [3H]inositol phosphates and Ins(1,4,5)P3 levels in cardiac atria and ventricles ? a comparative study

Abstract

In this study incorporation of [3H]inositol into inositol phosphates and phosphoinositides as well as tissue Ins(1,4,5)P3 levels of the atria and ventricles of isolated, perfused rat hearts were compared. Although the incorporation of [3H]inositol into the phosphoinositides of atria and ventricles was similar, significantly higher (2-3 fold) incorporation rates into inositol phosphates were observed in atrial tissue. Using a D-myo-[3H]Ins(1,4,5)P3 assay system, the Ins(1,4,5)P3 levels observed in atria from perfused rat hearts were also significantly higher than those obtained under the same experimental circumstances in the ventricles. Since previous studies on whole hearts showed inhibition of the phosphatidylinositol (PI) pathway during ischaemia with an immediate significant stimulation upon reperfusion [12, 20], the effects of ischaemia and 1 min postischaemic reperfusion were also examined separately in atria and ventricles. The results showed that 20 min of global ischaemia significantly depressed Ins(1,4,5)P3 levels as well as incorporation of [3H]inositol into ventricular InsP2 and InsP3. Reperfusion caused an immediate (within 1 min) increase in Ins(1,4,5)P3 levels and also [3H]inositol incorporation into all three cytosolic inositol phosphates in the ventricles. However, the effect of ischaemia and reperfusion on Ins(1,4,5)P3 levels as well as the incorporation of [3H]inositol into the inositol phosphates were less prominent in the atria. It therefore appears that the differential responses of the atria and the ventricles to an oxygen deficiency [41] are also reflected in the differences in PI metabolism during ischaemia-reperfusion.

Inositol‐1,4,5‐trisphosphate‐dependent Ca2+ signalling in cat atrial excitation–contraction coupling and arrhythmias

“…Although IP 3 ‐dependent Ca 2+ release in cardiac tissue was demonstrated early on (Hirata et al 1984; Fabiato, 1986; Nosek et al 1986), the role of IP 3 in E‐C coupling and cardiac function in the adult mammalian heart has remained highly controversial (Marks, 2000; Bers, 2001; Blatter et al 2003). There is evidence that IP 3 ‐dependent signalling may be important during development (Rosemblit et al 1999; Poindexter et al 2001) and cardiac injury (Mouton et al 1992; Jacobsen et al 1996; Woodcock et al 1997, 1998; Harrison et al 1998; Yamada et al 2001), or may be relevant to the regulation of specific cellular functions such as propagation of electrical signals in Purkinje fibres, regulation of organellar and nuclear membrane permeability, Ca 2+ ‐dependent gene transcription, cardiac hypertrophy signalling and cell growth (e.g. Jaconi et al 2000; for references see Bers, 2001).…”

l-Arginine, a nitric oxide precursor, attenuates ischemia-reperfusion injury by inhibiting inositol-1,4,5-triphosphate

“…The relationship between IP3 and Ca in our results suggests that increased IP3 induced more Ca accumulation, resulting in reperfusion injury. [25][26][27][28] We now consider the mechanism by which NO reduces IP3 after reperfusion. As an intracellular messenger, NO activates sGC, which causes an increase in cGMP concentration.…”