Glial Ca(2+)signaling links endocytosis to K(+) buffering around neuronal somas to regulate excitability

Glial-neuronal signaling at synapses is widely studied, but how glia interact with neuronal somas to regulate their activity is unclear. Drosophila cortex glia are restricted to brain regions devoid of synapses, providing an opportunity to characterize interactions with neuronal somas. Mutations in the cortex glial NCKX(zydeco) elevate basal Ca(2+), predisposing animals to seizure-like behavior. To determine how cortex glial Ca(2+) signaling controls neuronal excitability, we performed an in vivo modifier screen of the NCKX(zydeco) seizure phenotype. We show that elevation of glial Ca(2+) causes hyperactivation of calcineurin-dependent endocytosis and accumulation of early endosomes. Knockdown of sandman, a K(2P) channel, recapitulates NCKX(zydeco) seizures. Indeed, sandman expression on cortex glial membranes is substantially reduced in NCKX(zydeco) mutants, indicating enhanced internalization of sandman predisposes animals to seizures. These data provide an unexpected link between glial Ca(2+) signaling and the well-known role of glia in K(+) buffering as a key mechanism for regulating neuronal excitability.