MEF-2 repression of GEM-4/Copine expression decreases muscle excitability by increasing gap junction coupling

Activity induced gene expression promotes behavioral plasticity (including several forms of learning and memory) by altering synaptic connectivity and neuron excitability. While several transcriptional targets modify synapses, little is known about targets regulating excitability. Here, we identify a single MEF-2 and CRH-1/CREB transcriptional target, gem-4/Copine, whose expression increases the excitability of C. elegans body muscles. In muscles, gem-4 expression is repressed by MEF-2 and is induced by CRH-1. GEM-4 expression in muscles decreases the number of gap junctions, thereby increasing membrane resistance and excitability. These results identify activity induced copine expression as a mechanism to control gap junction coupling and excitability.