Rapid neuromodulation by cortisol in the rat paraventricular nucleus: an in vitro study.
1. We have used a range of in vitro electrophysiological techniques to investigate the mechanism of rapid cortisol neuromodulation of parvocellular neurones in the rat paraventricular nucleus. 2. In our study, we found that cortisol (10 microM) increased spontaneous action-current firing frequency to 193%. This effect was insensitive to the glucocorticoid intracellular-receptor antagonist mifepristone. 3. Cortisol (0.1-10 microM) had no detectable effects on whole-cell GABA current amplitudes, or GABA(A) single-channel kinetics. 4. Cortisol (10 microM) inhibited whole-cell potassium currents in parvocellular neurones by shifting the steady-state activation curve by 14 mV to the right. 5. Additionally, in a cell line expressing both the glucocorticoid intracellular receptor and recombinant, fast inactivating potassium channels (hKv1.3), cortisol (1 and 10 microM) inhibited potassium currents by shifting their steady-state activation curves to the right by 12 mV (10 microM cortisol). This effect was also insensitive to the cortisol antagonist, mifepristone. 6. These data suggest that inhibition of voltage-gated potassium channels may contribute to the rapid neuromodulatory effects of cortisol, possibly by direct interaction with the ion channel itself.
Department of Physiology, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT.
Abu
A
Zaki
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R
Barrett-Jolley
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D006727:Hormone Antagonists / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology*; D066298:In Vitro Techniques; D051664:Kv1.3 Potassium Channel; D015735:Mifepristone / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology; D011965:Receptors, Glucocorticoid / Q000378:metabolism
D006727:Hormone Antagonists; C496975:Kcna3 protein, rat; D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D018079:Receptors, GABA; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D006854:Hydrocortisone