Abstract
Potassium leak channels are essential to neurophysiological function. Leaks suppress excitability through maintenance of resting membrane potential below the threshold for action potential firing. Conversely, voltage-dependent potassium channels permit excitation because they do not interfere with rise to threshold, and they actively promote recovery and rapid re-firing. Previously attributed to distinct transport pathways, we demonstrate here that phosphorylation of single, native hippocampal and cloned KCNK2 potassium channels produces reversible interconversion between leak and voltage-dependent phenotypes. The findings reveal a pathway for dynamic regulation of excitability.
Highlights
Departments of Pediatrics and Cellular and Molecular Physiology, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, Connecticut 06536, USA
KCNK2-like channels were not observed in small on-cell patches with undifferentiated cells (n = 46), but were apparent with mature cells in 5 of 20 patches having only one to three channels. (Seventeen other patches had too many channels to evaluate, and 111 were quiet; to reduce activity of other native channels, long pre-pulse depolarizations were used to silence channels subject to inactivation, and pipette and bath solutions contained magnesium at physiological concentration (1 mM) magnesium and no sodium or calcium.) When native KCNK2-like channels were excised from cells in inside-out mode and treated with the catalytic sub-unit of protein kinase A (PKA) (20 U/ml) and ATP (1 mM), they showed a decrease in activity at –60 mV
Potassium channels that are active at rest inhibit depolarization toward firing threshold, and suppress excitation
Summary
Departments of Pediatrics and Cellular and Molecular Physiology, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, Connecticut 06536, USA. Leaks suppress excitability through maintenance of resting membrane potential below the threshold for action potential firing. Attributed to distinct transport pathways, we demonstrate here that phosphorylation of single, native hippocampal and cloned KCNK2 potassium channels produces reversible interconversion between leak and voltage-dependent phenotypes. Cloning of TOK1 from Saccharomyces cerevisiae[15], KCNK0 from Drosophila melanogaster[16] and, to date, twelve mammalian KCNK genes for 2 P domain potassium-selective leak channels, has affirmed that these currents are carried by dedicated pathways amenable to detailed study[17]. We report that the single canonical site in KCNK2 for protein kinase A (PKA) phosphorylation, previously shown to mediate temperature sensitivity[20], controls the amount of channel activity, but its fundamental response to voltage
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