Pb2+ inhibits the hyperpolarization-activated current in acutely isolated dorsal root ganglion neurons

The hyperpolarization-activated h channel current (Ih) reported to be present in acutely isolated rat dorsal root ganglion (DRG) neurons is inhibited by Cs+ and ZD7288. It was recently reported that lead (Pb2+) inhibits voltage-gated Ca2+ and K+ channels in DRG neurons but the effect of Pb2+ on Ih has so far not been reported. Using whole-cell patch clamp technique we show that Pb2+ specifically inhibited Ih. External application of 0.1, 1 and 10 microM Pb2+ reversibly reduced the amplitude of Ih in a dose-dependent manner, with an IC50 value of 3.7 microM and a Hill coefficient of 1.1. Pb2+ shifted the activation curve of Ih by 9.3 mV but had no effect on the slope factor. Pb2+ inhibited Ih in a voltage-dependent manner and slowed down the activation process, indicating an action of Pb2+ on the activation kinetics of h channels. Our studies thus demonstrated that Pb2+ is a dose-dependent, voltage-dependent and reversible blocker of Ih in DRG neurons.