Low affinity block of native and cloned hyperpolarization-activated Ih channels by Ba 2+ ions

Abstract

Ba 2+ 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 Ba 2+, whereas the hyperpolarization-activated cation current, I h, is assumed not to be sensitive to Ba 2+. Here we investigated the effects of Ba 2+ 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 Ba 2+ reduce the maximal I h conductance (IC 50∼3–5 mM) in both CA1 pyramidal neurons and in HEK 293 cells without specificity for HCN1 or HCN2 subunits. In addition, Ba 2+ 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 Ba 2+. The combined results suggest that Ba 2+, 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.