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SODIUM CHANNELS (NAV1.2/B1) EXPRESSED IN XENOPUS OOCYTES DEMONSTRATE SENSITIVITY TO PYRETHROIDS.
Citation:
MEACHAM, C. A., J. WATKINS, K. M. CROFTON, AND T. J. SHAFER. SODIUM CHANNELS (NAV1.2/B1) EXPRESSED IN XENOPUS OOCYTES DEMONSTRATE SENSITIVITY TO PYRETHROIDS. Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Description:
Voltage-sensitive sodium channels (VSSCs) are hypothesized to be a primary target of pyrethroid insecticides. However, multiple isoforms of VSSCs exist and the sensitivity of different isoforms to pyrethroids has not been well characterized. The Nav1.2/1 channel predominates in adult central neurons and has previously been reported to be sensitive to cypermethrin, a Type II pyrethroid, but insensitive to the Type I pyrethroids permethrin and cismethrin (Smith and Soderlund, Neurotoxicology 19:823-832, 1998). The present experiments sought to examine the sensitivity of Nav1.2/?1 channels to additional Type I and II pyrethroids. Xenopus laevis oocytes were injected with rat (Nav1.2) and 1 subunit mRNA. Sodium currents elicided by a 45 msec step depolarization to -10 mV from a holding potential of -100 mV were recorded using two-electrode voltage clamp techniques. Tetrodotoxin (1 M) blocked both peak and tail sodium currents. Pyrethroids (10 M) were applied to the oocytes in ND96 buffer, and the percent increase in tail current amplitude was determined. Type II pyrethroids (deltamethrin (257% increase over control), fenpropathrin (156%), cypermethrin (105%), esfenvalerate (205%), and -cyfluthrin (197%)) increased tail currents, while Type I pyrethroids (tetramethrin (2%), permethrin (3%)) did not (n=5-7 oocytes/compound). These results demonstrate that the
Nav1.2/1 rat sodium channel, when expressed in Xenopus oocytes, is sensitive to Type II, but not Type I pyrethroids. (This is an abstract of a proposed presentation and does not necessarily reflect EPA policy).