A novel action of deltamethrin on membrane resistance in mammalian skeletal muscle and non-myelinated nerve fibres.
The pyrethroids, deltamethrin and cismethrin, were assessed for their ability to change membrane conductance directly in skeletal muscle and indirectly in non-myelinated nerve fibre preparations from the rat. In diaphragm muscle fibres of the rat, input resistance was significantly increased (35%) by deltamethrin but not by cismethrin, compared with solvent alone. In perfused vagus nerve from the rat, the amplitude of the post-tetanic hyperpolarization was significantly increased (100%) by deltamethrin both in vitro and ex vivo but not by cismethrin or solvent. In both test systems the actions of deltamethrin were abolished by changing the perfusate to a low chloride solution. The enhancement of amplitude of post-tetanic hyperpolarization by deltamethrin was reversed by ivermectin, a compound known to increase the resting chloride flux in neuronal preparations. Depolarizing afterpotentials, indicative of a prolongation in sodium conductance, did not develop until 0.5-1.0 hr after the enhancement of the amplitude of post-tetanic hyperpolarization by deltamethrin in the vagus preparations. The amplitude of post-tetanic hyperpolarization was not enhanced by exposure of the vagus to veratrine. These observations reinforce the conclusion that the enhancement of post-tetanic hyperpolarization by deltamethrin is not the result of intracellular accumulation of sodium. In addition, the chloride-dependent nature of the effects of deltamethrin, in both muscle and non-myelinated nerve, suggests that they are in both cases due to a reduction in resting membrane chloride conductance. This novel action of deltamethrin would be expected to amplify the effect of prolonged sodium current and thus influence the actions on excitable membranes both directly and indirectly.
Forshaw
P J
PJ
M.R.C. Toxicology Unit, M.R.C. Laboratories, Carshalton, Surrey, U.K.
Ray
D E
DE
D000818:Animals; D003964:Diaphragm / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects; D009186:Myelin Sheath / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D009570:Nitriles; D011722:Pyrethrins / Q000494:pharmacology*; D051381:Rats; D012132:Respiratory Muscles / Q000187:drug effects*; D014630:Vagus Nerve / Q000187:drug effects
D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin; C017498:cismethrin