Leptin-induced dynamic alterations in the actin cytoskeleton mediate the activation and synaptic clustering of BK channels Dervla O’Malley, Andrew J. Irving and Jenni Harvey 1 Neuroscience Institute, Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK 1 Correspondence: E-mail: j.z.harvey@dundee.ac.uk <h3>SPECIFIC AIMS</h3> Because previous studies have shown that the activity of both peripheral and neuronal BK channels can be regulated by actin dynamics, we examined the role of the actin cytoskeleton in the activation of hippocampal BK channels by the hormone leptin. PI 3-kinase links leptin receptor activation to stimulation of BK channels and subsequent inhibition of hippocampal hyperexcitability. To determine the downstream targets of PI 3-kinase and whether leptin receptor driven changes in the levels of PtdIns(3,4,5)P 3 drive the alterations in actin dynamics, we assessed the effects of leptin on the subcellular distribution of PtdIns(3,4,5)P 3 and BK channels in hippocampal neurons. <h3>PRINCIPAL FINDINGS</h3> <h3>1. PI 3-kinase-driven disassembly of actin filaments underlies activation of BK channels by leptin</h3> Using cell-attached recording techniques, we examined the effects of stabilizing actin filaments with jasplakinolide on the ability of leptin to activate BK channels in hippocampal neurons. In neurons exposed to jasplakinolide (10
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Leptin-induced dynamic alterations in the actin cytoskeleton mediate the activation and synaptic clustering of BK channels
OMalley, Dervla; Irving, Andrew J.; Harvey, Jenni
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, Volume 19 (13): 1917
Fed of American Socs for Experimental Biology – Nov 1, 2005
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