Abstract
It is usually understood that Ca2+-activated Ca2+ release (CICR) is a Ca release from ryanodine receptors. However, a CICR from IP3 receptors (IP3Rs) has also been described and characterized in hippocampus (Nakamura et al., 1999; Power and Sah, 2002) and visual cortex pyramidal cells (Yamamoto et al., 2000). In this particular form of CICR, which we call IP3-assisted CICR, IP3Rs are activated beforehand by IP3 but kept closed, until opening is finally triggered by action potential-induced Ca2+ inflow through vlotage-dependent Ca channels (VDCCs). We have shown that IP3-assisted CICR enhances SK channel current and thereby reducing neural excitability (Yamamoto et al, 2002; Yamada et al, 2004). In these previous experiments, the IP3-mobilizing neurotransmitter that we used was either the muscarinic acetylcholine receptor agonist carbachol or the group I metabotropic glutamate receptor agonist DHPG. Both of them were effective at 10uM but ineffective at 5uM. Whether these two drugs co-applied together, each at an innefective dose by itself, result in the effective enhancement of SK current is presumable but not self-evident. We have demonstrated that this is the case, suggesting that IP3 produced by different G-protein coupled receptors is additive in the cytosol and that IP3-mobilizing ligands may be synergistic in various cellular contexts. [J Physiol Sci. 2008;58 Suppl:S76]
