Short- and long-term roles of phosphatidylinositol 4,5-bisphosphate PIP2 on Cav3.1- and Cav3.2-T-type calcium channel current

Abstract T-type calcium (Ca 2+ ) channels play important physiological functions in excitable cells including cardiomyocyte. Phosphatidylinositol-4,5-bisphosphate (PIP 2 ) has recently been reported to modulate various ion channels' function. However the actions of PIP 2 on the T-type Ca 2+ channel remain unclear. To elucidate possible effects of PIP 2 on the T-type Ca 2+ channel, we applied patch clamp method to investigate recombinant Ca V 3.1- and Ca V 3.2-T-type Ca 2+ channels expressed in mammalian cell lines with PIP 2 in acute- and long-term potentiation. Short- and long-term potentiation of PIP 2 shifted the activation and the steady-state inactivation curve toward the hyperpolarization direction of Ca V 3.1-I Ca.T without affecting the maximum inward current density. Short- and long-term potentiation of PIP 2 also shifted the activation curve toward the hyperpolarization direction of Ca V 3.2-I Ca.T without affecting the maximum inward current density. Conversely, long-term but not short-term potentiation of PIP 2 shifted the steady-state inactivation curve toward the hyperpolarization direction of Ca V 3.2-I Ca.T . Long-term but not short-term potentiation of PIP 2 blunted the voltage-dependency of current decay Ca V 3.1-I Ca.T . PIP 2 modulates Ca V 3.1- and Ca V 3.2-I Ca.T not by their current density but by their channel gating properties possibly through its membrane-delimited actions.