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Article

Wei Zhou^*, Francisco S. Cayabyab^,, Peter S. Pennefather^,,||, Lyanne C. Schlichter^,, and Thomas E. DeCoursey^*

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

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 K_i = 40 µM, and the HERG-selective blocker, E-4031, blocked with K_i = 37 nM. Implications of the presence of HERG-like K⁺ channels for the ontogeny of microglia are discussed.

Key Words: human ether-à-go-go-related gene • inward rectifier • ion channels • inactivation • erg

Abbreviations: _K, Nernst potential for K⁺; g_K, K⁺ conductance; HERG, human ether-à-go-go-related gene (erg) and its product; IR, inwardly rectifying K⁺ channel

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This article has been cited by other articles:

				P. S. Pennefather, W. Zhou, and T. E. DeCoursey Idiosyncratic Gating of HERG-like K+ Channels in Microglia J. Gen. Physiol., June 1, 1998; 111(6): 795 - 805. [Abstract] [Full Text] [PDF]

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