I am having real trouble patching hippocampal CA1 neurones. I am blind patching and every time I patch onto a cell the holding current rises to about -300 pA. It's driving me insane. The input resistance also decreases simultaneously. It seems to happen directly after my cell 'opens up' (ie. my series resistance becomes ridiculously low; 5 MOhms). Has anyone experienced anything similar. Is it osmolarity, temperature, movement of pippette... I am losing my mind. Please contact me.