POTASSIUM CHANNEL MODULATION BY THE PSEUDOPEPTIDE OCHRATOXIN-A IN RATNERVE-FIBERS

Ochratoxin A (OTA), a naturally occurring mycotoxin produced by Asperg illus and Penicillium genera, blocks anion conductance in Madin-Darby canine kidney (MDCK) cells and reduces the potassium concentration gra dient in the same cells, So far, a direct effect of OTA on cation chan nels has not been reported. Experiments were then designed to explore the OTA action on ion channels of rat nerve fibres, Voltage clamp tech nique has shown that OTA (0.1-1 mu M) does not significantly affect so dium current in the intact myelinated axon. After paranodal demyelinat ion (using 0.2% pronase) large K+ outward and K+ tail currents are eli cited upon depolarization and repolarization, OTA application on prona se treated fibres produces the following effects: 1) reduction in the amplitude of the tail current with a negligible effect on the time con stant of its fast decaying component (modified by pronase application) ; 2) reduction in potassium conductance to 30% of the control value (i .e,, the value in pronase-treated fibres); and 3) reduction in the lea kage conductance, Our findings point at the paranodal region of myelin ated nerve fibres as a target for the neurotoxic pseudopeptide OTA fou nd as contaminant in food. The uncleaved OTA is effectively acting sin ce pronase fails to cleave it into phenylalanine and OT alpha. J, Neur osci, Res. 53:312-317, 1998, (C) 1998 Wiley-Liss, Inc.