Gln49-PLA(2) is a phospholipase A(2) isolated from the Gloydius ussurensis snake venom. In this paper, we studied its effect on the function of neural conduction. Electrophysiological studies demonstrated that Gln49-PLA(2) reduced the amplitude of the action potential and the velocity of nerve conduction on isolated mouse sciatic nerve. Patch clamp recordings confirmed that Gln49-PLA(2) significantly decreased neural excitability by the potentiation of sodium channels and the blockade of potassium channels in nerve terminal. In freshly isolated hippocampal pyramidal neurons, 54.25% of potassium current was inhibited by 20 mu g/ml Gln49-PLA(2). However, sodium current was potentiated by 158.99% under the same condition. These findings demonstrate that the effect of Gln49-PLA(2) on ion channels is the main mechanism of analgesic action.