Current transients associated with BK channels in human glioma cells.
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, Itransient, activated and inactivated rapidly (approximately 1 ms). The I-V relationship of Itransient had features that were inconsistent with simple ionic current through open ion channels: (i) Itransient amplitude peaked with a -80 mV voltage change and was invariant over a 200 mV range, and (ii) Itransient remained large and outward at -140 mV. We provide evidence for a direct relationship of Itransient 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 Itransient seen over time were often perfectly in phase. Substituting intracellular K+ with Cs+, Li+, or Na+ ions reversibly reduced Itransient and BK currents. Itransient was not observed in recordings of other BK currents (hbr5 expressed in HEK cells and BK currents in rat neurons), suggesting Itransient is unique to BK currents in human glioma cells. We conclude that Itransient 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.
Ransom
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CB
Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA.
Liu
X
X
Sontheimer
H
H
D000222:Adaptation, Physiological; D001693:Biological Transport, Active; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D005910:Glioma / Q000503:physiopathology*; D006801:Humans; D015640:Ion Channel Gating; D007668:Kidney / Q000196:embryology / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials; D011188:Potassium / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*
D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011188:Potassium