Action of dexmedetomidine on rat locus coeruleus neurones: intracellular recording in vitro

doi:10.1016/0014-2999(95)00417-J

European Journal of Pharmacology

Volume 285, Issue 3, 24 October 1995, Pages 261-268

https://doi.org/10.1016/0014-2999(95)00417-J Get rights and content

Abstract

The action of dexmedetomidine on rat locus coeruleus neurones was examined using intracellular recordings from the in vitro brain slice preparation. Concentrations of dexmedetomidine from 1 to 1000 nM were tested. At 30 nM, dexmedetomidine produced complete inhibition of firing of all neurones tested (n = 21); this was associated with a 13 mV hyperpolarization (range 2.2–29.7 mV, n = 21) and a 27% reduction in input resistance (range 11.1–46.2%, n = 17). The dexmedetomidine responses reached a plateau phase between 100 and 1000 nM. Based on single-cell recordings, the hyperpolarizing potency of dexmedetomidine was found to be 6 times greater than that of clonidine (n = 10). The reversal potential for the dexmedetomidine-induced hyperpolarization was − 106.9 ± 1.7 mV (n = 9), a value similar to the K⁺ equilibrium potential; hyperpolarization was blocked by both CsCl and BaCl₂. The effect of dexmedetomidine was antagonized by yohimbine, with a dissociation equilibrium constant of 30 nM. In contrast, prazosin, the α₁-, α_2B- and α_2C-adrenoceptor subtype-preferring ligand, did not inhibit the dexmedetomidine effect. Our results also show that low concentrations of oxymetazoline (10–300 nM), an α_2A-adrenoceptor subtype-selective drug, cause profound inhibition of neuronal activity in the locus coeruleus. These data therefore suggest that dexmedetomidine binds to α_2A-adrenoceptors on the cell membrane of neurones of the locus coeruleus and that this leads to opening of the inwardly rectifying K⁺ channels, resulting in the observed hyperpolarization of the membrane.

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The α2-adrenoceptor agonist dexmedetomidine acts on the locus coeruleus to induce sedation. It also has an analgesic effect without causing respiratory depression (Gerlach and Dasta, 2007; Chiu et al., 1995). In addition, intravenous (IV) administration of dexmedetomidine prolongs the duration of spinal anesthesia (Elcicek et al., 2010).
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Regular paperAction of dexmedetomidine on rat locus coeruleus neurones: intracellular recording in vitro

Abstract

Neuropharmacology

Trends Pharmacol. Sci.

Eur. J. Pharmacol.

Neuropharmacology

Brain Res.

Br. J. Anaesth.

Progr. Brain Res.

Br. J. Anaesth.

J. Clin. Anesth.

Brain Res.

Br. J. Anaesth.

Progr. Neurobiol.

Pain

Progr. Brain Res.

Brain Res.

Eur. J. Pharmacol.

Neuroscience

α2-Adrenoceptor-mediated, hyperpolarization of locus coeruleus neurons: intracellular studies in vivo

Science

The locus coeruleus: neurobiology of a central noradrenergic nucleus

Progr. Neurobiol.

Locus coeruleus activity in vitro: intrinsic regulation by a calcium-dependent potassium conductance but not α2-adrenoceptors

J. Neurosci.

Opiate-and α2-adrenoceptor-induced hyperpolarizations of locus coeruleus neurons in brain slices: reversal by cyclic adenosine 3′:5′-monophosphate analogues

J. Neurosci.

Regular paper
Action of dexmedetomidine on rat locus coeruleus neurones: intracellular recording in vitro

α₂-Adrenoceptor-mediated, hyperpolarization of locus coeruleus neurons: intracellular studies in vivo

Locus coeruleus activity in vitro: intrinsic regulation by a calcium-dependent potassium conductance but not α₂-adrenoceptors

Opiate-and α₂-adrenoceptor-induced hyperpolarizations of locus coeruleus neurons in brain slices: reversal by cyclic adenosine 3′:5′-monophosphate analogues