Abstract: AimTo explore the modulation of Salvia miltiorrhiza on hyperpolarization-activated current (I_h) channels in dorsal root ganglion (DRG) neurons of rats and identify the mechanism of Salvia miltiorrhiza in alleviating pain and inhibiting calcium overload. MethodsThe effect of Salvia miltiorrhiza injection on I_h channels in DRG neurons of rats were examined by using whole-cell patch clamp technique. ResultsThe experimental results showed that the amplitude of I_h evoked by -150 mV was (-1.06±0.18) nA. The I_h could be fitted well into the single kinetics and the time constant of activation, τ was clearly voltage-dependent with τ=(322.14±28.81) ms at -100 mV, decreasing to τ=(62.51±9.78) ms at -150 mV. The reversal potential of I_h was (-35.03±1.12) mV measured from tail currents. But no significant differences were found between the DRG neurons in the absence and presence of Salvia miltiorrhiza injection (10%, 25%, 50%) in the current amplitude, the time constant of activation and the reversal potential. The only difference between the DRG neurons in the absence and presence of Salvia miltiorrhiza injection was the half-activation potential of I_h. In control recordings the half-activation potential was (-106.07±3.59) mV. By comparison, the half-activation potentials changed to (-111.59±3.79) mV (n=31 neurons, P<0.05), (-119.37±4.96) mV (n=31 neurons, P<0.05) and (-121.23±3.86) mV (n=31 neurons, P<0.05) in the presence of 10%, 25%, 50% Salvia miltiorrhiza injection, respectively. ConclusionOnly the half-activation potential of I_h in the arthritic and neuropathic rat models shifted in the depolarizing direction, which increased the electrophysiological activity of I_h and made it related to peripheral hyperalgesia. The selective inhibition of Salvia miltiorrhiza on the electrophysiological activity of I_h may be one of the mechanisms underlying its analgesic effects.