Figure 6: Coumaphos oxon has a biphasic effect on ACh responses.
From: Cholinergic pesticides cause mushroom body neuronal inactivation in honeybees
The effects of coumaphos oxon on baseline IM and ACh responses were investigated under voltage clamp. (a) Coumaphos oxon (200 nM) initially potentiates ACh responses (10 min after application), consistent with AChE inhibition. Subsequently, coumaphos oxon evokes a tonic current and inhibits ACh responses (30 min after application). (b) The time course of the effect of coumaphos oxon on IM in a different KC. The tonic current develops slowly and is reversed by d-TC, consistent with nAChR activation by accumulated endogenous ACh. (c) Mean (±s.e.m.) data showing the biphasic effect (initial potentiation followed by sustained inhibition) of coumaphos oxon (n=11, *P<0.01, paired t-test) on ACh responses. Included for comparison is the effect of the widely used AChE inhibitor donepezil (n=7, *P<0.01, paired t-test). (d) Mean (±s.e.m.) data showing the effects of coumaphos oxon (n=11) and donepezil (n=7) on IM (*P<0.01, paired t-test). Inhibition of ACh responses is associated with an increase in IM (tonic current). (e) Mean (±s.e.m.) data showing that the time course of the biphasic effect of coumaphos oxon on ACh responses is dependent on concentration (0.05 μM, n=4; 0.2 μM, n=3; 1 μM, n=4; *P<0.01, unpaired t-test). (f) Mean (±s.e.m.) data showing that the parent compound coumaphos inhibits ACh responses at concentrations ≥10 μM (1 μM, n=3; 10 μM, n=5; 50 μM, n=3; *P<0.05, paired t-test). The effect of 0.5% ethanol, the vehicle for the highest coumaphos concentration, is included as a control. (g) Example ACh responses before and after coumaphos (10 μM) application. (h) The time course of the effect of coumaphos on ACh responses in a different KC. Coumaphos (10–50 μM) inhibits ACh responses without significantly changing IM (−1.3±1.5 pA, n=8) or ACh response kinetics, consistent with a lack of AChE inhibition.
