摘要：The sensitivity of many ion channels to phosphatidylinositol-4,5-bisphosphate (PIP2) levels in the cell membrane suggests that PIP2 fluctuations are important and general signals modulating neuronal excitability. Yet the PIP2 dynamics of central neurons in their native environment remained largely unexplored. Here, we examined the behavior of PIP2 concentrations in response to activation of Gq-coupled neurotransmitter receptors in rat CA1 hippocampal neurons in situ in acute brain slices. Confocal microscopy of the PIP2-selective molecular sensors tubbyCT-GFP and PLCδ1-PH-GFP showed that pharmacological activation of muscarinic acetylcholine (mAChR) or group I metabotropic glutamate (mGluRI) receptors induces transient depletion of PIP2 in the soma as well as in the dendritic tree. The observed PIP2 dynamics were receptor-specific, with mAChR activation inducing stronger PIP2 depletion than mGluRI, whereas agonists of other Gαq-coupled receptors expressed in CA1 neurons did not induce measureable PIP2 depletion. Furthermore, the data show for the first time neuronal receptor-induced oscillations of membrane PIP2 concentrations. Oscillatory behavior indicated that neurons can rapidly restore PIP2 levels during persistent activation of Gq and PLC. Electrophysiological responses to receptor activation resembled PIP2 dynamics in terms of time course and receptor specificity. Our findings support a physiological function of PIP2 in regulating electrical activity.
