HERG-LIKE K+ CHANNELS IN MICROGLIA

A voltage-gated K+ conductance resembling that of the human ether-a-go -go-related gene product (HERG) was studied using whole-cell voltage-c lamp recording, and found to be the predominant conductance at hyperpo larized potentials in a cell line (MLS-9) derived from primary culture s of rat microglia. Its behavior differed markedly from the classical inward rectifier K+ currents described previously in microglia, but cl osely resembled HERG currents in cardiac muscle and neuronal tissue. T he HERG-like channels opened rapidly on hyperpolarization from 0 mV, a nd then decayed slowly into an absorbing closed state. The peak K+ con ductance-voltage relation was half maximal at -59 mV with a slope fact or 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 b y making the holding potential progressively more positive than more n eg negative. The origin of this hysteresis is explored in a companion paper (Pennefather, P.S., W. Zhou, and T.E. DeCoursey. 1998. J. Gen. P hysiol. 111:795-805). The pharmacological profile of the current diffe red from classical inward rectifier but closely resembled HERG. Block by Cs+ or Ba2+ occurred only at millimolar concentrations, La3+ blocke d with K-i = similar to 40 mu M, and the HERG-selective blocker, E-403 1, blocked with K-i = 37 nM. Implications of the presence of HERG-like K+ channels for the ontogeny of microglia are discussed.