Nuclear BK Channels Regulate Gene Expression via the Control of Nuclear Calcium Signaling

Ion channels are essential for the regulation of neuronal functions. The significance of plasma membrane, mitochondrial, endoplasmic reticulum, and lysosomal ion channels in the regulation of Ca(2+) is well established. In contrast, surprisingly less is known about the function of ion channels on the nuclear envelope (NE). Here we demonstrate the presence of functional large-conductance, calcium-activated potassium channels (BK channels) on the NE of rodent hippocampal neurons. Functionally blockade of nuclear BK channels (nBK channels) induces NE-derived Ca(2+) release, nucleoplasmic Ca(2+) elevation, and cAMP response element binding protein (CREB)-dependent transcription. More importantly, blockade of nBK channels regulates nuclear Ca(2+)-sensitive gene expression and promotes dendritic arborization in a nuclear Ca(2+)-dependent manner. These results suggest that nBK channel functions as a molecular linker between neuronal activity and nuclear Ca(2+) to convey the signals from synapse to nucleus and is a new modulator for synaptic activity-dependent neuronal functions at the NE level.