Pharmacodynamics of potassium channel openers in cultured neuronal networks

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Article discussing pharmacodynamics of potassium channel openers in cultured neuronal networks.

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8 p.

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Wu, Calvin; Gopal, Kamakshi V.; Lukas, Thomas J.; Gross, Guenter W. & Moore, Ernest J. June 5, 2014.

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Article discussing pharmacodynamics of potassium channel openers in cultured neuronal networks.

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8 p.

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Abstract: A novel class of drugs – potassium (K+) channel openers or activators – has recently been shown to cause anticonvulsive and neuroprotective effects by activating hyperpolarizing K+ currents, and therefore, may show efficacy for treating tinnitus. This study presents measurements of the modulatory effects of four K+ channel openers on the spontaneous activity and action potential waveforms of neuronal networks. The networks were derived from mouse embryonic auditory cortices and grown on microelectrode arrays. Pentylenetetrazol was used to create hyperactivity states in the neuronal networks as a first approximation for mimicking tinnitus or tinnitus-like activity. We then compared the pharmacodynamics of the four channel activators, retigabine and flupirtine (voltage-gated K+ channel KV7 activators), NS1619 and isopimaric acid (“big potassium” BK channel activators). The EC50 of retigabine, flupirtine, NS1619, and isopimaric acid were 8.0, 4.0, 5.8, and 7.8 µM, respectively. The reduction of hyperactivity compared to the reference activity was significant. The present results highlight the notion of re-purposing the K+ channel activators for reducing hyperactivity of spontaneously active auditory networks, serving as a platform for these drugs to show efficacy toward target identification, prevention, as well as treatment of tinnitus.

Copyright © 2014 Elsevier Science Ltd., all rights reserved. http://dx.doi.org/10.1016/j.ejphar.2014.03.017

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  • European Journal of Pharmacology, 2014, New York: Elsevier Science Ltd., pp. 68-75

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  • Publication Title: European Journal of Pharmacology
  • Volume: 732
  • Page Start: 68
  • Page End: 75
  • Peer Reviewed: Yes

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UNT Scholarly Works

Materials from the UNT community's research, creative, and scholarly activities and UNT's Open Access Repository. Access to some items in this collection may be restricted.

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  • June 5, 2014

Added to The UNT Digital Library

  • June 6, 2014, 11:19 a.m.

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  • April 1, 2015, 3:21 p.m.

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Wu, Calvin; Gopal, Kamakshi V.; Lukas, Thomas J.; Gross, Guenter W. & Moore, Ernest J. Pharmacodynamics of potassium channel openers in cultured neuronal networks, article, June 5, 2014; [New York, New York]. (digital.library.unt.edu/ark:/67531/metadc287994/: accessed December 15, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT College of Arts and Sciences.