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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Tartaglia, L. A. et al. Cell 83, 1263–1271 (1995).
Spanswick, D., Smith, M. A., Groppi, V. E., Logan, S. D. & Ashford, M. L. J. Nature 390, 521–525 (1997).
Harvey, J., McKenna, F., Herson, P. S., Spanswick, D. & Ashford, M. L. J. J. Physiol. 504, 527–535 (1997).
Franciolini, F. Biochim. Biophys. Acta 943, 419–427 (1988).
Wann, K. T. & Richards, C. D. Eur. J. Neurosci. 6, 607–617 (1994).
Toro, L., Wallner, M., Meera, P. & Tanaka, Y. News Physiol. Sci. 13, 112–117 (1998).
Latorre, R. Acta. Physiol. Scand. Suppl. 582, 13 (1989).
Harvey, J. et al. J. Biol. Chem. 275, 4660–4669 (2000).
Shanley, L. J., Irving, A. J. & Harvey, J. J. Neurosci. 21, RC186 (1–6) (2001).
Cowley, M. A. et al. Nature 411, 480–484 (2001).
Powis, J. E., Bains, J. S. & Ferguson, A. V. Am. J. Physiol. 274, R1468–R1472 (1998).
Behrens, R. et al. FEBS Lett. 474, 99–106 (2000).
Meera, P., Wallner, M. & Toro, L. Proc. Natl. Acad. Sci . 97, 5562–5567 (2000).
Acknowledgements
This work is supported by The Wellcome Trust (grant nos. 055291 & 042726). J.H. is a Wellcome RCD Fellow.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nn824
This article is cited by
-
Leptin: role over central nervous system in epilepsy
BMC Neuroscience (2018)
-
Leptin alters somatosensory thalamic networks by decreasing gaba release from reticular thalamic nucleus and action potential frequency at ventrobasal neurons
Brain Structure and Function (2018)
-
Leptin as a Neuroprotector and a Central Nervous System Functional Stability Factor
Neuroscience and Behavioral Physiology (2015)
-
Effects of leptin on pedunculopontine nucleus (PPN) neurons
Journal of Neural Transmission (2013)
-
Ghrelin and leptin secretion in patients with moderate Alzheimer's disease
The Journal of nutrition, health and aging (2012)