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Current Transients Associated with BK Channels in Human Glioma Cells

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Abstract

We have previously demonstrated the expression of BK channels in human glioma cells. There was a curious feature to the whole-cell currents of glioma cells seen during whole-cell patch-clamp: large, outward current transients accompanied repolarization of the cell membrane following an activating voltage step. This transient current, I transient, activated and inactivated rapidly (≈1 ms). The I-V relationship of I transient had features that were inconsistent with simple ionic current through open ion channels: (i) I transient amplitude peaked with a −80 mV voltage change and was invariant over a 200 mV range, and (ii) I transient remained large and outward at −140 mV. We provide evidence for a direct relationship of I transient to glioma BK currents. They had an identical time course of activation, identical pharmacology, identical voltage-dependence, and small, random variations in the amplitude of the steady-state BK current and I transient seen over time were often perfectly in phase. Substituting intracellular K+ with Cs+, Li+, or Na + ions reversibly reduced I transient and BK currents. I transient was not observed in recordings of other BK currents (hbr5 expressed in HEK cells and BK currents in rat neurons), suggesting I transient is unique to BK currents in human glioma cells. We conclude that I transient is generated by a mechanism related to the deactivation, and level of prior activation, of glioma BK channels. To account for these findings we propose that K+ ions are “trapped” within glioma BK channels during deactivation and are forced to exit to the extracellular side in a manner independent of membrane potential.

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Acknowledgements

This work was supported by National Institutes of Neurological Diseases and Stroke Grant NS-36692 and American Cancer Society Grant RPG-97-083-01CDD (H.S.). C.B.R. was supported by a Medical Scientist Training Program scholarship. The authors appreciate the discussions and comments of Drs. Robin Lester, Michael Quick, and David Weiss.

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  1. Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA

    C. B. Ransom, X. Liu & H. Sontheimer

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  1. C. B. Ransom
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  2. X. Liu
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  3. H. Sontheimer
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Correspondence to H. Sontheimer.

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Ransom, C., Liu, X. & Sontheimer, H. Current Transients Associated with BK Channels in Human Glioma Cells . J. Membrane Biol. 193, 201–213 (2003). https://doi.org/10.1007/s00232-003-2019-7

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  • DOI: https://doi.org/10.1007/s00232-003-2019-7

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