Effects of the pyrethroid cypermethrin on l-glutamate-induced changes in the input conductance of the ventrolateral muscles of the larval house fly, Musca domestica

Abstract

Cypermethrin has been previously demonstrated to block neuromuscular transmission in larval house fly ventrolateral muscles (VLMs). Although the effect is consistent with a presynaptic depolarization as it involves an increase in miniature excitatory postsynaptic current frequency, and decrease in amplitude of evoked responses, the role of a postsynaptic action in the production of these responses has not yet been assessed. Thus, this study was undertaken to observe the effects of both cypermethrin and its solvent acetone upon the postsynaptic aspect of synaptic transmission. VLMs 6a and 7a had similar resting membrane potentials (−57.6 ± 8.0 mV and −59.2 ± 8.3 mV, respectively; n = 20 cells) and input conductances (3.08 ± 0.87 and 2.97 ± 1.00 × 10 −7 siemens, respectively; n = 12 cells). l-Glutamate produced a dose-dependent depolarization and increase in the sarcolemma input conductance. A Hill plot revealed that a minimum of one glutamate molecule was required to bind to each receptor to elicit a unit response. At concentrations of 1 ml liter −1 acetone and 10 n M cypermethrin, no effects were observed on the muscle resting membrane potential, the sarcolemma input conductance, or sensitivity to 10 m M l-glutamate (pretreated with 1 μ M concanavalin A to block glutamate receptor desensitization). However, at higher concentrations both acetone and cypermethrin had postsynaptic effects. Acetone (10 ml liter −1) caused a slight increase in muscle input resistance ( P < 0.05), although higher concentrations produced a decrease in input resistance (EC 50 at 4%) of up to 70% control values. A transient membrane depolarization was observed upon initial application of acetone (> 10 ml liter −1) which was followed by a sustained membrane hyperpolarization. Intense axonal repetitive firing was also noted with acetone concentrations above 10 ml liter −1. Cypermethrin (1 μ M), 30–90 min after application, blocked the l-glutamate induced increases in input conductance and caused substantial oscillations in the sarcolemma resting membrane potential. The initial membrane depolarizations induced by 10 m M l-glutamate in control preparations were still observed in muscles poisoned with 1 μ M cypermethrin. These data demonstrate that the block of neuromuscular transmission at larval house fly nerve terminals by 10 n M cypermethrin does not involve a change in muscle membrane input conductance or a decrease in receptor sensitivity to glutamate, and therefore is likely to be a consequence of its presynaptic action.