BK channels with beta3a subunits generate use-dependent slow afterhyperpolarizing currents by an inactivation-coupled mechanism.
Large-conductance, Ca2+- and voltage-activated K+ (BK) channels are broadly expressed proteins that respond to both cellular depolarization and elevations in cytosolic Ca2+. The characteristic functional properties of BK channels among different cells are determined, in part, by tissue-specific expression of auxiliary beta subunits. One important functional property conferred on BK channels by beta subunits is inactivation. Yet, the physiological role of BK channel inactivation remains poorly understood. Here we report that as a consequence of a specific mechanism of inactivation, BK channels containing the beta3a auxiliary subunit exhibit an anomalous slowing of channel closing. This produces a net repolarizing current flux that markedly exceeds that expected if all open channels had simply closed. Because of the time dependence of inactivation, this behavior results in a Ca2+-independent but time-dependent increase in a slow tail current, providing an unexpected mechanism by which use-dependent changes in slow afterhyperpolarizations might regulate electrical firing. The physiological significance of inactivation in BK channels mediated by different beta subunits may therefore arise not from inactivation itself, but from the differences in the amplitude and duration of repolarizing currents arising from the beta-subunit-specific energetics of recovery from inactivation.
Zeng
Xu-Hui
XH
Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Benzinger
G Richard
GR
Xia
Xiao-Ming
XM
Lingle
Christopher J
CJ
D002118:Calcium / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000737:chemistry* / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008956:Models, Chemical; D011188:Potassium / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000502:physiology
D051036:Large-Conductance Calcium-Activated Potassium Channels; D021122:Protein Subunits; D011188:Potassium; D002118:Calcium