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Actions of BRL 34915 (Cromakalim) upon convulsive discharges in guinea pig hippocampal slices

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Summary

The effects of the purported K+ channel opener BRL 34915 upon CNS neurons were examined in guinea pig hippocampal slices. Both the EPSP component and the population spike of field potentials recorded in the CA1 area were reduced in amplitude by BRL 34915 (EC50 about 100 μmol/l). In the same concentration range, BRL 34915 also slowed down the bursting rate of pacemaker neurons in the CA3 region. In order to test a possible anticonvulsant efficacy of the drug, the excitability of hippocampal neurons was increased experimentally by changing the ionic composition of the perfusion medium (omission of Ca2+ or Mg2+, elevation of K+). In all three conditions, epileptiform neuronal activity occurred, which was depressed by BRL 34915. The similarity of the effects of BRL 34915 in normal and convulsive slices indicates that the compound acts upon intrinsic nonsynaptic processes controlling neuronal excitability and cell firing.

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References

  • Allen SL, Boyle JP, Cortijo J, Foster RW, Morgan GP, Small RC (1986) Electrical and mechanical effects of BRL 34915 in guinea-pig isolated trachealis. Br J Pharmacol 89:395–405

    Google Scholar 

  • Anderson WA, Lewis DV, Swartzwelder HS, Wilson WA (1986) Magnesium-free medium activates seizure-like events in the rat hippocampal slice. Brain Res 398:215–219

    Google Scholar 

  • Ashton D, Willems R, Deprins E, Wauquier A (1987) The effects of anticonvulsants on synaptic and non-synaptic epileptogenesis, and on inhibition in the guinea-pig hippocampus. Neuroscience 22:Suppl 1997P

  • Bragdon AC, Taylor DM, Wilson WA (1986) Potassium-induced epileptiform activity in area CA3 varies markedly along the septotemporal axis of the rat hippocampus. Brain Res 378:169–173

    Google Scholar 

  • Cain CR, Metzler V (1985) Electrophysiological effects of the anti-hypertensive agent BRL 34915 on guinea-pig papillary muscle. Naunyn-Schmiedeberg's Arch Pharmacol 329:R53

    Google Scholar 

  • Clapham JC, Wilson C (1986) Effects of the novel antihypertensive agent BRL 34915 in comparison with nifedipine on rabbit isolated mesenteric artery. Br J Pharmacol Suppl 87:77P

  • Coldwell MC, Howlett DR (1987) Specifity of action of the novel antihypertensive agent, BRL 34915, as a potassium channel activator — comparison with nicorandil. Biochem Pharmacol 36:3663–3669

    Google Scholar 

  • Conder ML, McCullough JR (1987) Purported K-channel opener, BRL 34915, blocks inwardly rectifying K-current in isolated guinea-pig ventricular myocytes. Biophys J 51:258a

    Google Scholar 

  • Galvan M, Grafe P, ten Bruggencate G (1982) Convulsant actions of 4-aminopyridine on the guinea-pig olfactory cortex slice. Brain Res 241:75–86

    Google Scholar 

  • Hamilton TC, Weir SW, Weston AH (1986) Comparison of the effects of BRL 34915 and verapamil on electrical and mechanical activity in rat portal vein. Br J Pharmacol 88:103–111

    Google Scholar 

  • Heinemann U, Franceschetti S, Hamon B, Konnerth A, Yaari Y (1985) Effects of anticonvulsants on spontaneous epileptiform activity which develops in the absence of chemical synaptic transmission in hippocampal slices. Brain Res 325:349–352

    Google Scholar 

  • Hollingsworth M, Amedee T, Edwards D, Mironneau J, Savincau JP, Small RC, Weston AH (1987) The relaxant action of BRL 34915 in rat uterus. Br J Pharmacol 91:803–813

    Google Scholar 

  • Hood TW, Siegfried J, Haas HL (1983) Analysis of carbamazepine actions in hippocampal slices of the rat. Cell Mol Neurobiol 3:213–222

    Google Scholar 

  • Jefferys JGR, Haas HL (1982) Synchronized bursting of CA1 hippocampal pyramidal cells in the absence of synaptic transmission. Nature 300:448–450

    Google Scholar 

  • Korn SJ, Giacchino JL, Chamberlin NL, Dingledine R (1987) Epileptiform burst activity induced by potassium in the hippocampus and its regulation by GABA-mediated inhibition. J Neurophysiol 57:325–340

    Google Scholar 

  • Matsumoto H, Ajmone-Marsan C (1964) Cortical cellular phenomena in experimental epilepsy: interictal manifestations. Exp Neurol 9:286–304

    Google Scholar 

  • Mody I, Lambert JDC, Heinemann U (1987) Low extracellular magnesium induces epileptiform activity and spreading depression in rat hippocampal slices. J Neurophysiol 57:869–888

    Google Scholar 

  • Olpe HR, Baudry M, Jones RSG (1985) Electrophysiological and neurochemical investigations on the action of carbamazepine on the rat hippocampus. Eur J Pharmacol 110:71–80

    Google Scholar 

  • Prince D (1978) Neurophysiology of epilepsy. Annu Rev Neurosci 1:395–415

    Google Scholar 

  • Quast U (1987) Effect of the K+ efflux stimulating vasodilator BRL 34915 on 86Rb+ efflux and spontaneous activity in guinea-pig portal vein. Br J Pharmacol 91:569–578

    Google Scholar 

  • Rose GM, Olpe HR, Haas HL (1986) Testing of prototype antiepileptics in hippocampal slices. Naunyn-Schmiedeberg's Arch Pharmacol 332:89–92

    Google Scholar 

  • Rutecki PA, Lebeda FJ, Johnston D (1985) Epileptiform activity induced by changes in extracellular potassium in hippocampus. J Neurophysiol 54:1363–1374

    Google Scholar 

  • Shetty SS, Weiss GB (1987) Dissociation of actions of BRL 34915 in the rat portal vein. Eur J Pharmacol 141:485–488

    Google Scholar 

  • Southerton JS, Taylor SG, Weston AH (1987) Comparison of the effects of BRL 34915 and of acetylcholine-liberated EDRF on rat aorta. J Physiol (Lond) 382:50P

    Google Scholar 

  • Stanton PK, Jones RSG, Mody I, Heinemann U (1987) Epileptiform activity induced by lowering extracellular Mg2+ in combined hippocampal-entorhinal cortex slices: modulation by receptors for norepinephrine and N-methyl-D-aspartate. Epilepsy Res 1:53–62

    Google Scholar 

  • Taylor CP, Dudek FE (1982) Synchronous neural after discharges in rat hippocampal slices without active chemical synapses. Science 218:810–812

    Google Scholar 

  • Weir SW, Weston AH (1986a) Effect of apamin on responses to BRL 34915, nicorandil and other relaxants in the guinea-pig taenia caeci. Br J Pharmacol 88:113–120

    Google Scholar 

  • Weir SW, Weston AH (1986b) The effects of BRL 34915 and nicorandil on electrical and mechanical activity and on 86Rb efflux in rat blood vessels. Br J Pharmacol 88:121–128

    Google Scholar 

  • Weston AH, Abbott A (1987) New class of antihypertensive acts by opening K+ channels. TIPS 8:282–284

    Google Scholar 

  • Wong RKS, Prince DA (1978) Participation of calcium spikes during intrinsic burst firing in hippocampal neurons. Brain Res 159:385–390

    Google Scholar 

  • Yaari Y, Konnerth A, Heinemann U (1986) Nonsynaptic epileptogenesis in the mammalian hippocampus in vitro. II. Role of extracellular potassium. J Neurophysiol 56:424–438

    Google Scholar 

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Alzheimer, C., ten Bruggencate, G. Actions of BRL 34915 (Cromakalim) upon convulsive discharges in guinea pig hippocampal slices. Naunyn-Schmiedeberg's Arch Pharmacol 337, 429–434 (1988). https://doi.org/10.1007/BF00169535

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