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We apply electric fields at different frequencies of 0.1,1,10 and 100kHz to the rat basophilic leukemia (RBL)mast cells in calcium-containing or calcium-free buffers.The stimuli cause changes of the intracellular calcium ion concentration [Ca2+]i as well as the histamine.The [Ca2+]i increases when the frequency of the exteal electric field increases from 100 Hz to 10kHz,and then decreases when the frequency further increases from 10kHz to 100kHz,showing a peak at 100kHz.A similar frequency dependence of the histamine release is also found.The [Ca2+]i and the histamine releases at 100Hz are about the same as the values of the control group with no electrical stimulation.The ruthenium red (RR),an inhibitor to the TRPV (transient receptor potential (TRP) family V) channels across the cell membrane,is used in the experiment to check whether the electric field stimuli act on the TRPV channels.Under an electric field of 10kHz,the [Ca2+]i in a calcium-concentration buffer is about 3.5 times as much as that of the control group with no electric stimulation,while the [Ca2+]i in a calcium-free buffer is only about 2.2 times.Similar behavior is also found for the histamine release.RR blockage effect on the [Ca2+]i decrease is statistically significant (~75%) when mast cells in the buffer with calcium are stimulated with a 10 kHz electric field in comparison with the result without the RR treatment.This proves that TRPVs are the channels that calcium ions inflow through from the extracellular environment under electrical stimuli.Under this condition,the histamine is also released following a similar way.We suggest that,as far as an electric stimulation is conceed,an application of ac electric field of 10 kHz is better than other frequencies to open TRPV channels in mast cells,and this would cause a significant calcium influx resulting in a significant histamine release,which could be one of the mechanisms for electric therapy.