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Nature Neuroscience 12, 745–750 (1 June 2009) | doi:10.1038/nn.2313

Na+-activated K+ channels express a large delayed outward current in neurons during normal physiology

Gonzalo Budelli , Travis A Hage , Aguan Wei , Patricio Rojas , Yuh-Jiin Ivy Jong , Karen O'Malley & Lawrence Salkoff

One of the largest components of the delayed outward current that is active under physiological conditions in many mammalian neurons, such as medium spiny neurons of the striatum and tufted-mitral cells of the olfactory bulb, has gone unnoticed and is the result of a Na+-activated K+ current. Previous studies of K+ currents in mammalian neurons may have overlooked this large outward component because the sodium channel blocker tetrodotoxin (TTX) is typically used in such studies. We found that TTX also eliminated this delayed outward component in rat neurons as a secondary consequence. Unexpectedly, we found that the activity of a persistent inward sodium current (persistent INa) is highly effective at activating this large Na+-dependent (TTX sensitive) delayed outward current. Using siRNA techniques, we identified SLO2.2 channels as being carriers of this delayed outward current. These findings have far reaching implications for many aspects of cellular and systems neuroscience, as well as clinical neurology and pharmacology.