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SouravNovember 9, 2024

How do neonicotinoid pesticides block synaptic transmission at cholinergic synapses in insects by binding to acetylcholine receptors?

How do neonicotinoid pesticides block synaptic transmission at cholinergic synapses in insects by binding to acetylcholine receptors?

Sourav
SouravNovember 9, 2024

Answer

Neonicotinoid pesticides block synaptic transmission at cholinergic synapses in insects primarily by binding to nicotinic acetylcholine receptors (nAChRs). This interaction disrupts normal neurotransmission, leading to severe physiological effects, including paralysis and death.

Mechanism of Action

  1. Binding to Nicotinic Acetylcholine Receptors:
    • Neonicotinoids, which are synthetic compounds similar to nicotine, selectively bind to the postsynaptic nAChRs in insects. These receptors are crucial for cholinergic signaling, which is the primary excitatory neurotransmission pathway in the insect nervous system.
  2. Agonistic Action:
    • Upon binding, neonicotinoids act as agonists, meaning they activate the receptors similarly to acetylcholine (ACh). However, their binding is often irreversible or leads to prolonged activation of the receptor. This results in continuous stimulation of the postsynaptic neuron.
  3. Disruption of Synaptic Transmission:
    • The persistent activation of nAChRs by neonicotinoids prevents ACh from effectively binding to these receptors. As a result, normal synaptic transmission is disrupted; the neurons become overstimulated initially but eventually lead to a state where they can no longer fire action potentials effectively, a phenomenon known as “depolarizing block.” This occurs because prolonged receptor activation can cause desensitization of nAChRs and inactivation of voltage-gated sodium channels necessary for action potential generation.
  4. Physiological Consequences:
    • The overstimulation and subsequent failure of synaptic transmission lead to paralysis and death in insects. The inability to transmit signals across synapses impairs essential functions such as movement and feeding, ultimately affecting survival.

Selectivity and Toxicity

  • Neonicotinoids are designed to selectively target insect nAChRs and exhibit much lower affinity for vertebrate receptors. This selectivity makes them relatively safe for mammals while being highly toxic to insects, which is a significant advantage in agricultural pest control. However, this selectivity has raised concerns about their impact on non-target species, particularly pollinators like bees, which are vital for ecosystem health and agricultural productivity

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