Low affinity block of native and cloned hyperpolanization-activated Ih channels by Ba2+ ions

Ba2+ is commonly used to discriminate two classes of ion currents. The classical inward-rectifying K+ current, I-Kir, is blocked by low millimolar concentrations of Ba2+, whereas the hyperpolarization-activated cation current, I-h, is assumed not to be sensitive to Ba2+. Here we investigated the effects of Ba2+ on I-h currents recorded from rat hippocampal CA1 pyramidal neurons. and on cloned I-h channels composed of either HCN1 or HCN2 subunits transiently expressed in Human Embryonic Kidney (HEK) 293 cells. The results show that low millimolar concentrations of Ba2+ reduce the maximal I-h conductance (IC(50)similar to3-5 mM) in both CA1 pyramidal neurons and in HEK 293 cells without specificity for HCN1 or HCN2 subunits. In addition, Ba2+ decreases the rate of activation and increases the rate of deactivation of I-h currents. Neither the half-maximal voltage of activation, V-h, nor the reversal potential of the I-h,channels were affected by Ba2+. The combined results suggest that Ba2+, at concentrations commonly used to block I-Kir currents, also reduces the conductance of I-h channels without subunit specificity, and affects the kinetics of I-h channel gating. (C) 2004 Elsevier B.V. All rights reserved.