Potassium channel modulation by the pseudopeptide ochratoxin A in rat nerve fibers.
Ochratoxin A (OTA), a naturally occurring mycotoxin produced by Aspergillus and Penicillium genera, blocks anion conductance in Madin-Darby canine kidney (MDCK) cells and reduces the potassium concentration gradient in the same cells. So far, a direct effect of OTA on cation channels has not been reported. Experiments were then designed to explore the OTA action on ion channels of rat nerve fibres. Voltage clamp technique has shown that OTA (0.1-1 microM) does not significantly affect sodium current in the intact myelinated axon. After paranodal demyelination (using 0.2% pronase) large K+ outward and K+ tail currents are elicited upon depolarization and repolarization. OTA application on pronase treated fibres produces the following effects: 1) reduction in the amplitude of the tail current with a negligible effect on the time constant 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 leakage conductance. Our findings point at the paranodal region of myelinated nerve fibres as a target for the neurotoxic pseudopeptide OTA found as contaminant in food. The uncleaved OTA is effectively acting since pronase fails to cleave it into phenylalanine and OT alpha.
Department of Pharmacology and Human Physiology, Medical School, University of Bari, Italy.
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Carratú
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Belmadani
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Cuomo
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Creppy
D000818:Animals; D002121:Calcium Channel Blockers / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003711:Demyelinating Diseases / Q000378:metabolism; D009186:Myelin Sheath / Q000737:chemistry / Q000502:physiology; D009412:Nerve Fibers / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D009793:Ochratoxins / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D011402:Pronase; D051381:Rats; D012584:Sciatic Nerve / Q000166:cytology; D012964:Sodium / Q000378:metabolism
D002121:Calcium Channel Blockers; D009793:Ochratoxins; D015221:Potassium Channels; C025589:ochratoxin A; D012964:Sodium; D011402:Pronase