Loss of expression of the fragile X mental retardation protein (FMRP) leads to the neurodevelopmental cognitive disorder fragile X syndrome (FXS). FMRP is known to modulate protein synthesis at the postsynaptic portion of synapses in the brain. Now, Pan-Yue Deng et al. identify a key role of FMRP in the presynaptic side of the synapse in regulating the duration of action potentials (Neuron 77, 696–711 ).

Credit: (BSIP / Science Source)

The researchers found that loss of FMRP could increase action potential duration within neurons in the hippocampus and cortex, two brain regions that modulate learning and memory. Reintroducing FMRP back into only the presynaptic neuron could restore normal action potentials, suggesting that FMRP is acting on the presynaptic side of the synapse.

Potassium channels are known to regulate action potential duration. Deng et al. found that neurons treated with blockers of BK potassium channels showed similar broadening of action potentials as neurons lacking FMRP. They showed that FMRP binds the regulatory subunit of BK channels to control the sensitivity of the channels to calcium. Neurons from mice lacking this regulatory subunit did not broaden their action potentials upon FMRP blockade.

Although the direct relevance of the findings to behavioral abnormalities in FXS still needs to be determined, these data suggest that activating BK channels could be beneficial in normalizing synaptic dysfunction in this disease.