The potent polyether brevetoxins produced by "K. brevis" activate voltage-sensitive sodium channels. Specifically, brevetoxins bind to site 5 on the alpha-subunit of voltage sensitive sodium channels (VSSCs), which serve as key proteins in the structure of the cell membrane. The binding of brevetoxin to VSSCs produces three key effects: a lowering of the activation potential to more negative values, the persistent activation of the channel and therefore repetitive firing of nerves, and the inability to reverse this prolonged mean open state. This leads to a number of health problems in both humans and animals alike. The disruption of normal sodium channel function namely results in massive fish kills and the poisoning of marine mammals and other aquatic invertebrates, which in turn are a source of human health problems as well. For instance, pulmonary receptors associated with ligand-gated epithelial Na+ channels and cathepsin inhibition in macrophages have been reported to be affected by brevetoxin exposure.