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Short- and long-term roles of phosphatidylinositol 4,5-bisphosphate PIP2 on Cav3.1- and Cav3.2-T-type calcium channel current
Authors:Yangong Liu  Tomohiro Iwano  Fangfang Ma  Pu Wang  Yan Wang  Mingqi Zheng  Gang Liu  Katsushige Ono
Institution:1. Department of Cardiology, The First Hospital of Hebei Medical University, 89 Donggang Road, Shijiazhuang, Hebei Province, 050031, People’s Republic of China;2. Department of Pathophysiology, Oita University School of Medicine, Yufu, Oita, 879-5593, Japan
Abstract: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 CaV3.1- and CaV3.2-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 CaV3.1-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 CaV3.2-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 CaV3.2-ICa.T. Long-term but not short-term potentiation of PIP2 blunted the voltage-dependency of current decay CaV3.1-ICa.T. PIP2 modulates CaV3.1- and CaV3.2-ICa.T not by their current density but by their channel gating properties possibly through its membrane-delimited actions.
Keywords:Phosphatidylinositol-4  T-type calcium channel  Corresponding author at: Department of Pathophysiology  Oita University School of Medicine  1-1 Idaigaoka  Hasama  Yufu  Oita  879-5593  Japan  
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