title: Nuclear BK channels regulate gene expression via the control of nuclear calcium signaling.
abstract: 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 little 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 cyclic AMP 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 the nBK channel functions as a molecular link between neuronal activity and nuclear Ca(2+) to convey signals from synapse to nucleus and is a new modulator, operating at the NE, of synaptic activity-dependent neuronal functions.
authors: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. [2] Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, Southern Medical University, Guangzhou, China.
authors: Boxing
authors: B
authors: Li
authors: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. [2] Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, Southern Medical University, Guangzhou, China.
authors: Wei
authors: W
authors: Jie
authors: School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China.
authors: Lianyan
authors: L
authors: Huang
authors: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. [2] Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, Southern Medical University, Guangzhou, China.
authors: Peng
authors: P
authors: Wei
authors: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. [2] Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, Southern Medical University, Guangzhou, China.
authors: Shuji
authors: S
authors: Li
authors: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. [2] Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, Southern Medical University, Guangzhou, China.
authors: Zhengyi
authors: Z
authors: Luo
authors: Department of Pharmacology and Systems Therapeutics, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Allyson K
authors: AK
authors: Friedman
authors: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors: Andrea L
authors: AL
authors: Meredith
authors: Department of Pharmacology and Systems Therapeutics, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Ming-Hu
authors: MH
authors: Han
authors: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. [2] Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, Southern Medical University, Guangzhou, China.
authors: Xin-Hong
authors: XH
authors: Zhu
authors: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. [2] Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, Southern Medical University, Guangzhou, China.
authors: Tian-Ming
authors: TM
authors: Gao
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000172:deficiency / Q000235:genetics*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009685:Nuclear Envelope / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; C465449:Kcnma1 protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels