Abstract
1. Intracellular recordings were obtained from a pontine slice preparation of the rat brain containing the locus coeruleus (LC). Two openers of ATP-sensitive potassium (K(ATP)) channels, RO 31-6930 (10 microM) and cromakalim (100 microM) decreased the spontaneous discharge of action potentials without altering their amplitude or duration. Neither compound changed the resting membrane potential. 2. Of two K(ATP) channel blockers, tolbutamide (300 microM) increased the firing rate, while glibenclamide (3 microM) only tended to do so. In addition, both compounds antagonized the effect of RO 31-6930 (10 microM). Neither glibenclamide (3 microM) nor tolbutamide (300 microM) altered the resting membrane potential. 3. Tetrodotoxin (0.5 microM) depressed the firing, but did not influence the inhibitory action of RO 31-6930 (10 microM). The excitatory amino acid antagonist, kynurenic acid (500 microM), did not change the spontaneous discharge of action potentials. 4. Small shifts (2-4 mV) of the membrane potential by hyper- or depolarizing current injections markedly decreased and increased the firing rate, respectively. 5. Noradrenaline (100 microM) hyperpolarized the cells and decreased their input resistance. This effect was not antagonized by glibenclamide (3 microM) or tolbutamide (300 microM). Ba2+ (2 mM), a blocker of both ATP-sensitive and inwardly rectifying potassium channels, abolished the effects of RO 31-6930 (10 microM) and noradrenaline (100 microM). 6. These data suggest that K(ATP) channels are present on the noradrenergic LC neurones, but are not coupled to alpha 2-adrenoceptors.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aghajanian G. K., VanderMaelen C. P. alpha 2-adrenoceptor-mediated hyperpolarization of locus coeruleus neurons: intracellular studies in vivo. Science. 1982 Mar 12;215(4538):1394–1396. doi: 10.1126/science.6278591. [DOI] [PubMed] [Google Scholar]
- Alzheimer C., Sutor B., ten Bruggencate G. Cromakalim (BRL 34915) acts on an inwardly rectifying neuronal K+ conductance, which is similar to that activated by adenosine. Pflugers Arch. 1989;414 (Suppl 1):S121–S122. doi: 10.1007/BF00582260. [DOI] [PubMed] [Google Scholar]
- Amoroso S., Schmid-Antomarchi H., Fosset M., Lazdunski M. Glucose, sulfonylureas, and neurotransmitter release: role of ATP-sensitive K+ channels. Science. 1990 Feb 16;247(4944):852–854. doi: 10.1126/science.2305257. [DOI] [PubMed] [Google Scholar]
- Ari Y. B., Lazdunski M. Galanin protects hippocampal neurons from the functional effects of anoxia. Eur J Pharmacol. 1989 Jun 20;165(2-3):331–332. doi: 10.1016/0014-2999(89)90732-2. [DOI] [PubMed] [Google Scholar]
- Ashcroft F. M. Adenosine 5'-triphosphate-sensitive potassium channels. Annu Rev Neurosci. 1988;11:97–118. doi: 10.1146/annurev.ne.11.030188.000525. [DOI] [PubMed] [Google Scholar]
- Ashcroft S. J., Ashcroft F. M. Properties and functions of ATP-sensitive K-channels. Cell Signal. 1990;2(3):197–214. doi: 10.1016/0898-6568(90)90048-f. [DOI] [PubMed] [Google Scholar]
- Ashford M. L., Boden P. R., Treherne J. M. Glucose-induced excitation of hypothalamic neurones is mediated by ATP-sensitive K+ channels. Pflugers Arch. 1990 Jan;415(4):479–483. doi: 10.1007/BF00373626. [DOI] [PubMed] [Google Scholar]
- Ashford M. L., Sturgess N. C., Trout N. J., Gardner N. J., Hales C. N. Adenosine-5'-triphosphate-sensitive ion channels in neonatal rat cultured central neurones. Pflugers Arch. 1988 Aug;412(3):297–304. doi: 10.1007/BF00582512. [DOI] [PubMed] [Google Scholar]
- Aston-Jones G., Shipley M. T., Chouvet G., Ennis M., van Bockstaele E., Pieribone V., Shiekhattar R., Akaoka H., Drolet G., Astier B. Afferent regulation of locus coeruleus neurons: anatomy, physiology and pharmacology. Prog Brain Res. 1991;88:47–75. doi: 10.1016/s0079-6123(08)63799-1. [DOI] [PubMed] [Google Scholar]
- Ben-Ari Y., Krnjević K., Crépel V. Activators of ATP-sensitive K+ channels reduce anoxic depolarization in CA3 hippocampal neurons. Neuroscience. 1990;37(1):55–60. doi: 10.1016/0306-4522(90)90191-6. [DOI] [PubMed] [Google Scholar]
- Bernardi H., Fosset M., Lazdunski M. Characterization, purification, and affinity labeling of the brain [3H]glibenclamide-binding protein, a putative neuronal ATP-regulated K+ channel. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9816–9820. doi: 10.1073/pnas.85.24.9816. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bott A., Eltze M., Illes P. External ATP antagonizes the effect of potassium channel openers in guinea-pig ventricular papillary muscle. Eur J Pharmacol. 1992 Mar 17;213(1):141–144. doi: 10.1016/0014-2999(92)90244-x. [DOI] [PubMed] [Google Scholar]
- Cedarbaum J. M., Aghajanian G. K. Catecholamine receptors on locus coeruleus neurons: pharmacological characterization. Eur J Pharmacol. 1977 Aug 15;44(4):375–385. doi: 10.1016/0014-2999(77)90312-0. [DOI] [PubMed] [Google Scholar]
- Cherubini E., North R. A., Williams J. T. Synaptic potentials in rat locus coeruleus neurones. J Physiol. 1988 Dec;406:431–442. doi: 10.1113/jphysiol.1988.sp017389. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Constanti A., Galvan M. Fast inward-rectifying current accounts for anomalous rectification in olfactory cortex neurones. J Physiol. 1983 Feb;335:153–178. doi: 10.1113/jphysiol.1983.sp014526. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cook N. S. The pharmacology of potassium channels and their therapeutic potential. Trends Pharmacol Sci. 1988 Jan;9(1):21–28. doi: 10.1016/0165-6147(88)90238-6. [DOI] [PubMed] [Google Scholar]
- Dunne M. J., Petersen O. H. Potassium selective ion channels in insulin-secreting cells: physiology, pharmacology and their role in stimulus-secretion coupling. Biochim Biophys Acta. 1991 Mar 7;1071(1):67–82. doi: 10.1016/0304-4157(91)90012-l. [DOI] [PubMed] [Google Scholar]
- Edwards G., Weston A. H. Structure-activity relationships of K+ channel openers. Trends Pharmacol Sci. 1990 Oct;11(10):417–422. doi: 10.1016/0165-6147(90)90149-3. [DOI] [PubMed] [Google Scholar]
- Egan T. M., Henderson G., North R. A., Williams J. T. Noradrenaline-mediated synaptic inhibition in rat locus coeruleus neurones. J Physiol. 1983 Dec;345:477–488. doi: 10.1113/jphysiol.1983.sp014990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gehlert D. R., Gackenheimer S. L., Mais D. E., Robertson D. W. Quantitative autoradiography of the binding sites for [125I] iodoglyburide, a novel high-affinity ligand for ATP-sensitive potassium channels in rat brain. J Pharmacol Exp Ther. 1991 May;257(2):901–907. [PubMed] [Google Scholar]
- Hamilton T. C., Weir S. W., Weston A. H. Comparison of the effects of BRL 34915 and verapamil on electrical and mechanical activity in rat portal vein. Br J Pharmacol. 1986 May;88(1):103–111. doi: 10.1111/j.1476-5381.1986.tb09476.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harms L., Finta E. P., Tschöpl M., Illes P. Depolarization of rat locus coeruleus neurons by adenosine 5'-triphosphate. Neuroscience. 1992 Jun;48(4):941–952. doi: 10.1016/0306-4522(92)90282-7. [DOI] [PubMed] [Google Scholar]
- Henderson G., Pepper C. M., Shefner S. A. Electrophysiological properties of neurons contained in the locus coeruleus and mesencephalic nucleus of the trigeminal nerve in vitro. Exp Brain Res. 1982;45(1-2):29–37. doi: 10.1007/BF00235760. [DOI] [PubMed] [Google Scholar]
- Henquin J. C., Meissner H. P. Opposite effects of tolbutamide and diazoxide on 86Rb+ fluxes and membrane potential in pancreatic B cells. Biochem Pharmacol. 1982 Apr 1;31(7):1407–1415. doi: 10.1016/0006-2952(82)90036-3. [DOI] [PubMed] [Google Scholar]
- Hicks G. A., Henderson G. Lack of evidence for coupling of the dopamine D2 receptor to an adenosine triphosphate-sensitive potassium (ATP-K+) channel in dopaminergic neurones of the rat substantia nigra. Neurosci Lett. 1992 Jul 20;141(2):213–217. doi: 10.1016/0304-3940(92)90897-g. [DOI] [PubMed] [Google Scholar]
- Häusser M. A., de Weille J. R., Lazdunski M. Activation by cromakalim of pre- and post-synaptic ATP-sensitive K+ channels in substantia nigra. Biochem Biophys Res Commun. 1991 Jan 31;174(2):909–914. doi: 10.1016/0006-291x(91)91504-6. [DOI] [PubMed] [Google Scholar]
- Illes P., Nörenberg W. Blockade of alpha 2-adrenoceptors increases opioid mu-receptor-mediated inhibition of the firing rate of rat locus coeruleus neurones. Naunyn Schmiedebergs Arch Pharmacol. 1990 Nov;342(5):490–496. doi: 10.1007/BF00169034. [DOI] [PubMed] [Google Scholar]
- Illes P., Regenold J. T. Omega-conotoxin GVIA and nifedipine inhibit Ca2+ action potentials in rat locus coeruleus neurons. Acta Physiol Scand. 1989 Nov;137(3):459–460. doi: 10.1111/j.1748-1716.1989.tb08778.x. [DOI] [PubMed] [Google Scholar]
- Kita T., Kita H., Kitai S. T. Electrical membrane properties of rat substantia nigra compacta neurons in an in vitro slice preparation. Brain Res. 1986 Apr 30;372(1):21–30. doi: 10.1016/0006-8993(86)91454-x. [DOI] [PubMed] [Google Scholar]
- Knöpfel T., Spuler A., Grafe P., Gähwiler B. H. Cytosolic calcium during glucose deprivation in hippocampal pyramidal cells of rats. Neurosci Lett. 1990 Sep 18;117(3):295–299. doi: 10.1016/0304-3940(90)90680-8. [DOI] [PubMed] [Google Scholar]
- Lacey M. G., Mercuri N. B., North R. A. On the potassium conductance increase activated by GABAB and dopamine D2 receptors in rat substantia nigra neurones. J Physiol. 1988 Jul;401:437–453. doi: 10.1113/jphysiol.1988.sp017171. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mourre C., Ben Ari Y., Bernardi H., Fosset M., Lazdunski M. Antidiabetic sulfonylureas: localization of binding sites in the brain and effects on the hyperpolarization induced by anoxia in hippocampal slices. Brain Res. 1989 May 1;486(1):159–164. doi: 10.1016/0006-8993(89)91288-2. [DOI] [PubMed] [Google Scholar]
- Mourre C., Widmann C., Lazdunski M. Specific hippocampal lesions indicate the presence of sulfonylurea binding sites associated to ATP-sensitive K+ channels both post-synaptically and on mossy fibers. Brain Res. 1991 Feb 1;540(1-2):340–344. doi: 10.1016/0006-8993(91)90533-2. [DOI] [PubMed] [Google Scholar]
- Nakaya H., Takeda Y., Tohse N., Kanno M. Effects of ATP-sensitive K+ channel blockers on the action potential shortening in hypoxic and ischaemic myocardium. Br J Pharmacol. 1991 May;103(1):1019–1026. doi: 10.1111/j.1476-5381.1991.tb12294.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Noma A. ATP-regulated K+ channels in cardiac muscle. Nature. 1983 Sep 8;305(5930):147–148. doi: 10.1038/305147a0. [DOI] [PubMed] [Google Scholar]
- Osmanović S. S., Shefner S. A. Anomalous rectification in rat locus coeruleus neurons. Brain Res. 1987 Aug 4;417(1):161–166. doi: 10.1016/0006-8993(87)90193-4. [DOI] [PubMed] [Google Scholar]
- Quayle J. M., Standen N. B., Stanfield P. R. The voltage-dependent block of ATP-sensitive potassium channels of frog skeletal muscle by caesium and barium ions. J Physiol. 1988 Nov;405:677–697. doi: 10.1113/jphysiol.1988.sp017355. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Regenold J. T., Illes P. Inhibitory adenosine A1-receptors on rat locus coeruleus neurones. An intracellular electrophysiological study. Naunyn Schmiedebergs Arch Pharmacol. 1990 Mar;341(3):225–231. doi: 10.1007/BF00169735. [DOI] [PubMed] [Google Scholar]
- Roeper J., Hainsworth A. H., Ashcroft F. M. Tolbutamide reverses membrane hyperpolarisation induced by activation of D2 receptors and GABAB receptors in isolated substantia nigra neurones. Pflugers Arch. 1990 Jun;416(4):473–475. doi: 10.1007/BF00370758. [DOI] [PubMed] [Google Scholar]
- Sanguinetti M. C., Scott A. L., Zingaro G. J., Siegl P. K. BRL 34915 (cromakalim) activates ATP-sensitive K+ current in cardiac muscle. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8360–8364. doi: 10.1073/pnas.85.21.8360. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmid-Antomarchi H., Amoroso S., Fosset M., Lazdunski M. K+ channel openers activate brain sulfonylurea-sensitive K+ channels and block neurosecretion. Proc Natl Acad Sci U S A. 1990 May;87(9):3489–3492. doi: 10.1073/pnas.87.9.3489. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmid-Antomarchi H., De Weille J., Fosset M., Lazdunski M. The receptor for antidiabetic sulfonylureas controls the activity of the ATP-modulated K+ channel in insulin-secreting cells. J Biol Chem. 1987 Nov 25;262(33):15840–15844. [PubMed] [Google Scholar]
- Silva N. L., Bunney B. S. Intracellular studies of dopamine neurons in vitro: pacemakers modulated by dopamine. Eur J Pharmacol. 1988 May 10;149(3):307–315. doi: 10.1016/0014-2999(88)90661-9. [DOI] [PubMed] [Google Scholar]
- Treherne J. M., Ashford M. L. The regional distribution of sulphonylurea binding sites in rat brain. Neuroscience. 1991;40(2):523–531. doi: 10.1016/0306-4522(91)90138-e. [DOI] [PubMed] [Google Scholar]
- Wallenstein S., Zucker C. L., Fleiss J. L. Some statistical methods useful in circulation research. Circ Res. 1980 Jul;47(1):1–9. doi: 10.1161/01.res.47.1.1. [DOI] [PubMed] [Google Scholar]
- Williams J. T., Bobker D. H., Harris G. C. Synaptic potentials in locus coeruleus neurons in brain slices. Prog Brain Res. 1991;88:167–172. doi: 10.1016/s0079-6123(08)63806-6. [DOI] [PubMed] [Google Scholar]
- Williams J. T., Henderson G., North R. A. Characterization of alpha 2-adrenoceptors which increase potassium conductance in rat locus coeruleus neurones. Neuroscience. 1985 Jan;14(1):95–101. doi: 10.1016/0306-4522(85)90166-6. [DOI] [PubMed] [Google Scholar]
- Williams J. T., North R. A., Tokimasa T. Inward rectification of resting and opiate-activated potassium currents in rat locus coeruleus neurons. J Neurosci. 1988 Nov;8(11):4299–4306. doi: 10.1523/JNEUROSCI.08-11-04299.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Weille J. R., Lazdunski M. Regulation of the ATP-sensitive potassium channel. Ion Channels. 1990;2:205–222. doi: 10.1007/978-1-4615-7305-0_6. [DOI] [PubMed] [Google Scholar]
