HERG-like K+ Channels in Microglia |
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| Authors: | Wei Zhou Francisco S. Cayabyab Peter S. Pennefather Lyanne C. Schlichter Thomas E. DeCoursey |
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| Affiliation: | From the *Department of Molecular Biophysics and Physiology, Rush Presbyterian St. Luke''s Medical Center, Chicago, Illinois 60612; ‡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 |
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| Abstract: | 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 −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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| Keywords: | human ether-à -go-go-related gene, inward rectifier, ion channels, inactivation, erg |
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