Lidocaine nonselectively inhibited hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents (I_h) in both large and small dorsal root ganglia (DRG) neurons. (A) I_h were recorded in large and/or small DRG neurons. For HCN1^−/− mice, I_h was almost eliminated in large neurons while the currents were preserved in small neurons. Lidocaine at 100 μM could inhibit I_h in both large and small DRG neurons. (B) Activation curves of HCN channel were recorded. In large DRG neurons of HCN1^−/− mice, activation curve of HCN channel was diminished, whereas in small neurons, activation curve of HCN channel was unaffected by HCN1 deletion. (C) Lidocaine reversibly inhibited HCN channel currents without selectivity between large (n = 5) and small (n = 6) neurons (estimated IC₅₀ = 82 ± 10 and 88 ± 9 μM, respectively. (D) Lidocaine at 100 μM significantly hyperpolarized half-maximal activation potential of I_h in large neurons (top), while without significant effect in small neurons (bottom).