HERG-like K+ Channels in Microglia

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 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.

Cloning and Functional Characterization of the Smooth Muscle Ether-a-go-go-related Gene K+ Channel

“…These features of HERG channel dictate its role in repolarization of the cardiac action potential and frequency-dependent modulation of the action potential duration (11). Recent studies also suggest that an inwardly rectifying K ϩ conductance that is active near the resting membrane potential of gastrointestinal smooth muscle cells (12,13), pituitary cells (14 -16), carotid body (15)(16)(17), and microglia (18) has properties similar to that of HERG channels. In these cells HERG conductance has been directly demonstrated in single cells, and in esophageal and stomach smooth muscle the presence of a "window" current within the range of the resting potential and depolarization and contraction by HERG channel blockers of whole tissue segments strongly suggest a role for ether-a-gogo-related gene K ϩ conductance in maintaining resting membrane potential (12).…”

Functional Expression of the Multidrug Resistance Protein 1 in Microglia

“…The cell line displays morphological and phenotypical attributes characteristic of microglia, including pinocytosis of dyes (diI-acetylated low-density lipoprotein or lucifer yellow) and staining for several microglia cell markers: isolectin B4 (100% of cells), OX-42 antibody (98%), and ED-1 antibody (99%). The cells were negative for characteristic markers of astrocytes (glial fibrillary acidic protein) and fibroblasts (fibronectin) (Zhou et al, 1998).…”

“…The microglia cell line (MLS-9) was derived from neopallia of 2-or 3-day-old Wistar rat pups, as described previously (Zhou et al, 1998;Cayabyab and Schlichter, 2002). Briefly, microglia were isolated by enzymatic dissociation of tissue, and cultured in endotoxin-free medium (Invitrogen, Burlington, ON, Canada) for 10 to 12 days without feeding.…”

Acceleration of human myoblast fusion by depolarization: graded Ca2+ signals involved

“…These unusual characteristics confer to HERG its peculiar electrophysiological properties. The HERG gene was shown to be expressed in the heart , and mRNA for HERG is present in a number of different species and tissues Arcangeli et al, 1995;Arcangeli et al, 1997;Shi et al, 1997;Bianchi et al, 1998;Zhou et al, 1998;Overholt et al, 2000).…”