Na+-activated K+ channels express a large delayed outward current in neurons during normal physiology.
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 I(Na)) 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.
Department of Anatomy, Washington University School of Medicine, St. Louis, Missouri, USA.
Gonzalo
G
Budelli
Travis A
TA
Hage
Aguan
A
Wei
Patricio
P
Rojas
Yuh-Jiin Ivy
YJ
Jong
Karen
K
O'Malley
Lawrence
L
Salkoff
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics*; D008564:Membrane Potentials / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering; D051381:Rats; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D015221:Potassium Channels; D034741:RNA, Small Interfering; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin