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Short- and long-term roles of phosphatidylinositol 4,5-bisphosphate PIP 2 on Cav3.1- and Cav3.2-T-type calcium channel current.
Pathophysiology : the Official Journal of the International Society for Pathophysiology 2018 December 2
T-type calcium (Ca2+ ) channels play important physiological functions in excitable cells including cardiomyocyte. Phosphatidylinositol-4,5-bisphosphate (PIP2 ) has recently been reported to modulate various ion channels' function. However the actions of PIP2 on the T-type Ca2+ channel remain unclear. To elucidate possible effects of PIP2 on the T-type Ca2+ channel, we applied patch clamp method to investigate recombinant CaV 3.1- and CaV 3.2-T-type Ca2+ channels expressed in mammalian cell lines with PIP2 in acute- and long-term potentiation. Short- and long-term potentiation of PIP2 shifted the activation and the steady-state inactivation curve toward the hyperpolarization direction of CaV 3.1-ICa.T without affecting the maximum inward current density. Short- and long-term potentiation of PIP2 also shifted the activation curve toward the hyperpolarization direction of CaV 3.2-ICa.T without affecting the maximum inward current density. Conversely, long-term but not short-term potentiation of PIP2 shifted the steady-state inactivation curve toward the hyperpolarization direction of CaV 3.2-ICa.T . Long-term but not short-term potentiation of PIP2 blunted the voltage-dependency of current decay CaV 3.1-ICa.T . PIP2 modulates CaV 3.1- and CaV 3.2-ICa.T not by their current density but by their channel gating properties possibly through its membrane-delimited actions.
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