Portal de Periódicos da CAPES

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

1997; Wiley; Volume: 122; Issue: 8 Linguagem: Inglês

10.1038/sj.bjp.0701541

1476-5381

Mark Connor, Susan Ingram, MacDonald J. Christie,

Neuroscience and Neuropharmacology Research

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‐NH 2 (CTOP). When LC neurones were voltage clamped to −60 mV, application of cortistatin caused an outward current in all cells examined ( n =44), with a pEC 50 of 6.62. SRIF also caused an outward current in all cells examined ( n =43), with a pEC 50 of 6.93. The outward currents caused by cortistatin in 2.5 m m extracellular K + reversed polarity at −106 mV, very close to the predicted K + reversal potential of −105 mV. Increasing extracellular K + to 10.5 m m 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. Continuous application of a high concentration of SRIF (1 μ m ) resulted in a decrease of the outward current to a steady level of 49% of the maximum response, with a t 1/2 of 131 s. Application of a high concentration of cortistatin (3 μ m ) during the desensitized portion of the SRIF response did not result in any further outward current. Continuous application of a high concentration of cortistatin (10 μ m ) resulted in a decrease of the outward current to a steady level of 42% of the maximum response with a t 1/2 of 114 s. Application of a high concentration of SRIF (3 μ m ) during the desensitized portion of the cortistatin response produced only a small outward current. Continuous application of cortistatin (3 μ m ) also resulted in a decrease of the outward current (by 43%, t 1/2 of 136 s) and application of a high concentration of CTOP (10 μ m ) during the desensitized portion of the cortistatin response did not produce any outward current. Continuous application of a high concentration of CTOP (10 μ m ) resulted in a decrease of the outward current to a steady level of 70% of the maximum response with a t 1/2 of 143 s. Application of a high concentration of cortistatin (3 μ m ) during the desensitized portion of the CTOP response did not result in any further outward current. The actions of cortistatin (300 n m –10 μ m ) were not affected by the opioid antagonist naloxone (10 μ m ). Application of met‐enkephalin during the desensitized portion of the response to a high concentration of cortistatin (3 μ m ) produced an outward current similar to that produced by met‐enkephalin application alone. Thus cortistatin efficaciously activates an inwardly rectifying K + conductance in LC neurones. These actions appear to be mediated by a population of SRIF receptors, at which CTOP is also an agonist. Cortistatin does not appear to be a ligand for μ‐opioid receptors in rat LC neurons.