Osmotic forces and gap junctions in spreading depression: A computational model

In a computational model of spreading depression (SD), ionic movement throu gh a neuronal syncytium of cells connected by gap junctions is described el ectrodiffusively. Simulations predict that SD will not occur unless cells a re allowed to expand in response to osmotic pressure gradients and K+ is al lowed to move through gap junctions. SD waves of [K+](out) approximate to 2 5 to approximate to 60 mM moving at approximate to2 to approximate to 18 mm /min are predicted over the range of parametric values reported in gray mat ter, with extracellular space decreasing up to approximate to 50%. Predicte d waveform shape is qualitatively similar to laboratory reports. The delaye d-rectifier, NMDA, BK, and Na+ currents are predicted to facilitate SD, whi le SK and A-type K+ currents and glial activity impede SD. These prediction s are consonant with recent findings that gap junction poisons block SD and support the theories that cytosolic diffusion via gap junctions and osmoti c forces are important mechanisms underlying SD.