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J. Gen. Physiol.,
Volume 111, Number 6, June 1, 1998 781-794
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From the * Department of Molecular Biophysics and Physiology, Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois 60612; A voltage-gated K+ conductance resembling that of the human ether-à-go-go-related gene product
(HERG) was studied using whole-cell voltage-clamp recording, and found to be the predominant conductance at
hyperpolarized potentials in a cell line (MLS-9) derived from primary cultures of rat microglia. Its behavior differed markedly from the classical inward rectifier K+ currents described previously in microglia, but closely resembled HERG currents in cardiac muscle and neuronal tissue. The HERG-like channels opened rapidly on hyperpolarization from 0 mV, and then decayed slowly into an absorbing closed state. The peak K+ conductance-voltage
relation was half maximal at
Playfair Neuroscience Unit, Toronto Hospital Research Institute, Toronto, Ontario M5T 2S8, Canada; § Department of Physiology,
University of Toronto, Toronto, Ontario M5S 1A1, Canada; and
Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S
2S2, Canada
59 mV with a slope factor of 18.6 mV. Availability, assessed by a hyperpolarizing test
pulse from different holding potentials, was more steeply voltage dependent, and the midpoint was more positive
(
14 vs.
39 mV) when determined by making the holding potential progressively more positive than more negative. The origin of this hysteresis is explored in a companion paper (Pennefather, P.S., W. Zhou, and T.E. DeCoursey. 1998. J. Gen. Physiol. 111:795-805). The pharmacological profile of the current differed from classical inward rectifier but closely resembled HERG. Block by Cs+ or Ba2+ occurred only at millimolar concentrations, La3+
blocked with Ki = ~40 µM, and the HERG-selective blocker, E-4031, blocked with Ki = 37 nM. Implications of the
presence of HERG-like K+ channels for the ontogeny of microglia are discussed.
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