Cortistatin increase of a potassium conductance in rat locus coeruleus in vitro

British Journal of Pharmacology
M ConnorMacDonald J Christie

Abstract

1. In this study we examined the effects of cortistatin, a putative endogenous ligand for somatostatin (SRIF) receptors, on the membrane properties of rat locus coeruleus (LC) neurones in vitro, by use of intracellular and whole cell patch clamp recording. We have compared the actions of cortistatin with those of SRIF and the SRIF analogue D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP). 2. When LC neurones were voltage clamped to -60 mV, application of cortistatin caused an outward current in all cells examined (n = 44), with a pEC50 of 6.62. SRIF also caused an outward current in all cells examined (n = 43), with a pEC50 of 6.93. 3. The outward currents caused by cortistatin in 2.5 mM extracellular K+ reversed polarity at -106 mV, very close to the predicted K+ reversal potential of -105 mV. Increasing extracellular K+ to 10.5 mM resulted in a shift of the reversal potential of +38 mV, a shift consistent with a K+ conductance. The conductance activated by cortistatin showed mild inward rectification. 4. Continuous application of a high concentration of SRIF (1 microM) resulted in a decrease of the outward current to a steady level of 49% of the maximum response, with a t1/2 of 131 s. Application of a high concentration of cort...Continue Reading

References

Aug 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·R MaurerD Roemer
Aug 1, 1995·Journal of Neurophysiology·R A TravagliJ T Williams
Dec 1, 1996·British Journal of Pharmacology·M ConnorM J Christie
Mar 6, 1997·Biochemical and Biophysical Research Communications·S FukusumiM Fujino

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Citations

Mar 4, 2000·Brain Research·M Sánchez-AlavezO Prospéro-García
Dec 16, 1998·European Journal of Pharmacology·V H NguyenM J Christie
Sep 30, 2000·Brain Research. Brain Research Reviews·A D Spier, L de Lecea
Jun 1, 2000·Regulatory Peptides·I SelmerP C Emson
Apr 1, 2008·Molecular and Cellular Endocrinology·Luis de Lecea
Sep 26, 2012·The European Journal of Neuroscience·Javier LlorenteChris P Bailey
Sep 21, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·I S HaslamN L Simmons
Jun 8, 2004·Endocrine Reviews·Aart J van der LelyEzio Ghigo
Jan 26, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Gracia MerinoJulio G Prieto
Jan 28, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Takako KatoYoshinobu Takakura
Jun 22, 1999·Journal of Neuroscience Research·J R CriadoL de Lecea
Sep 26, 2003·Biochimica Et Biophysica Acta·Lars Neisig MøllerJens Juul Holst

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