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Leptin inhibits rat hippocampal neurons via activation of large conductance calcium-activated K+ channels

Abstract

Leptin is an important circulating factor that regulates energy balance via the leptin receptor Ob-Rb1 in the hypothalamus. Ob-Rb activation may inhibit hypothalamic neurons by activating ATP-sensitive K+ channels (KATP channels)2. Here we show that leptin inhibits hippocampal neurons via phosphoinositide 3-kinase (PI3-kinase)–driven activation of large conductance, calcium-activated K+ channels (BK channels), but not KATP channels. This may be an important mechanism for regulating hippocampal excitability.

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Figure 1: Leptin hyperpolarizes hippocampal neurons via BK activation.
Figure 2: Leptin activates BK channels via a PI3-kinase–driven process.

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Acknowledgements

This work is supported by The Wellcome Trust (grant nos. 055291 & 042726). J.H. is a Wellcome RCD Fellow.

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Correspondence to Jenni Harvey.

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The authors declare no competing financial interests.

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Shanley, L., Irving, A., Rae, M. et al. Leptin inhibits rat hippocampal neurons via activation of large conductance calcium-activated K+ channels. Nat Neurosci 5, 299–300 (2002). https://doi.org/10.1038/nn824

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