BK channels and a cGMP-dependent protein kinase (PKG) function through independent mechanisms to regulate the tolerance of synaptic transmission to acute oxidative stress at the Drosophila larval neuromuscular junction.

A cGMP-dependent protein kinase (PKG) has previously been shown to regulate synaptic transmission at the Drosophila neuromuscular junction (NMJ) during acute oxidative stress, potentially through modulation of downstream K⁺ channel kinetics; however, the specific K⁺ channels through which PKG functions remains unclear. In this study, we hypothesized that PKG may be acting on calcium-activated large-conductance Slo K⁺ channels, or BK channels. We found that genetic elimination and pharmacological inhibition of BK channel conductance increases synaptic transmission tolerance to acute H₂O₂-induced oxidative stress. Furthermore, we discovered that activation of PKG in BK channel loss-of-function (Slo⁴) mutants significantly decreases time to stimulus-induced synaptic failure, providing the first evidence of PKG and BK channels functioning independently to control synaptic transmission tolerance to acute oxidative stress.

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