It has been found that Inositol 1,4,5-trisphosphate receptors (IP3Rs), which function as inositol 1,4,5-trisphosphate (IP3)-gated Ca2+ channels, are expressed in working cardiac myocytes (Nosek et al., 1986). In atrial cells, accumulated evidence shows that IP3R signalling is involved in arrhythmic activity (Li et al., 2005; Woodcock, Kistler & Ju, 2009). However, there is little direct evidence whether IP3Rs expression in adult mammalian sino-atrial node (SAN), the origin site of generating rhythm in the heart. In current studies, we quantified the level of the expression of IP3Rs in the SANs by using a new cell direct qPCR technique. We find that both centre and peripheral SANs expression of IP3Rs. We also studied the effect of IP3R agonist, such as endothelin-1, IP3-butyryloxymethyl ester (IP3-BM), and antagonist 2-aminoethoxy diphenylborate (2-APB), on intracellular Ca2+ of spontaneously firing sinoatrial node preparations. In the presence of 10 nM endothelin-1, the resting [Ca2+]i was increased by 36 ± 13 % (n = 5; P < 0.05) and the firing rate was increased by 20 ± 8 % (P < 0.05). The results were similar when IP3-BM was used. IP3R antagonist 2-APB reduced intracellular Ca2+ and slowed the firing rate. However, such effects were only seen in wild type but not in IP3R2 knock out mice. The localisation of IP3R2s and IP3 induced Ca2+ sparks also further support that that IP3Rs are involved in cardiac peacemaking through the release of Ca2+ from the intracellular Ca2+ stores that are near subsarcolemmal membrane.
Li X, Zima AV, Sheikh F, Blatter LA, Chen J. (2005) Endothelin-1-induced arrhythmogenic Ca2+ signaling is abolished in atrial myocytes of inositol-1,4,5-trisphosphate(IP3)-receptor type 2-deficient mice. Circ. Res. 96: 1274-81.
Nosek TM, Williams MF, Zeigler ST, Godt RE. (1986) Inositol trisphosphate enhances calcium release in skinned cardiac and skeletal muscle. Am. J. Physiol. 250: C807-C811.
Woodcock EA, Kistler PM, Ju YK. (2009) Phosphoinositide signalling and cardiac arrhythmias. Cardiovasc. Res. 82: 286-95.