The effects of Salvia Miltiorrhiza injection on hyperpolarization-activated current channels in dorsal root ganglion neurons of rats

摘要

To explore the mechanisms of Salvia Miltiorrhiza in alleviating pain and inhibiting calcium overload, using whole-cell patch-clamp technique, the effects of Salvia Miltiorrhiza injection on hyperpolarization-activated current (I_h) channels in dorsal root ganglion (DRG) neurons of rats were examined. The experimental results showed that the amplitude of I_h evoked by -150mV was -1.06±0.18 nA; the I_h could be fitted well to the two kinetics and the time constants of activation, τ_1 and τ_2 were clearly voltage-dependent with τ_1 341.71±49.48 ms and τ_2 = 342.54±47.80 ms at -100mV, decreasing to τ_1= 73.12±9.47 ms and τ_2 = 51.94±5.56 ms at -150mV; the reversal potential of I_h was -31.54±1.82 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±3.79mV (n=10 neurons, P < 0.05), -119.37±4.96 mV (n=10 neurons, P < 0.05) and to -121.23±3.86 mV (n=10 neurons, P < 0.05) in the presence of 10%, 25%, 50% Salvia Miltiorrhiza injection, respectively. As only the half-activation potential of 4 in the arthritic and neuropathic rat models shifted in the depolarizing direction, which increased the electrophysiological activity of I_h and made it be concerned with peripheral hyperalgesia, the selective inhibition of Salvia Miltiorrhiza on the electrophysiological activity of I_h may be one of the mechanisms underlying its analgetic effects. At the same time, I_h channel has been thought to play an important role in the firing neuron action potential, so the block of Salvia Miltiorrhiza on calcium channels was perhaps related to the effects of Salvia Miltiorrhiza on the action potential mediated by I_h channel.