Cell swelling increases the severity of spreading depression in Locusta migratoria.

Progressive accumulation of extracellular potassium ions can trigger propagating waves of spreading depression (SD), which are associated with dramatic increases in extracellular potassium levels ([K(+)]o) and arrest in neural activity. In the central nervous system the restricted nature of the extracellular compartment creates an environment that is vulnerable to disturbances in ionic homeostasis. Here we investigate how changes in the size of the extracellular space induced by alterations in extracellular osmolarity affect locust SD. We found that hypotonic exposure increased susceptibility to experimentally induced SD evidenced by a decrease in the latency to onset and period between individual events. Hypertonic exposure was observed to delay the onset of SD or prevent the occurrence altogether. Additionally, the magnitude of extracellular K(+) concentration ([K(+)]o) disturbance during individual SD events was significantly greater and they were observed to propagate more quickly under hypotonic conditions compared with hypertonic conditions. Our results are consistent with a conclusion that hypotonic exposure reduced the size of the extracellular compartment by causing cell swelling and thus facilitated the accumulation of K(+) ions. Lastly, we found that pharmacologically reducing the accumulation of extracellular K(+) using the K(+) channel blocker tetraethylammonium slowed the rate of SD propagation while increasing [K(+)]o through inhibition of the Na-K-2Cl cotransporter increased propagation rates. Overall our findings indicate that treatments or conditions that act to reduce the accumulation of extracellular K(+) help to protect against the development of SD and attenuate the spread of ionic disturbance adding to the evidence that diffusion of K(+) is a leading event during locust SD.