Sci. STKE, 1 May 2001
Ion Channels KCNK2 Is Both Dependent and Independent
Voltage-independent potassium (K+) leak channels provide resting conductances that decrease membrane excitability, thereby reducing the chance of spontaneous action potential firing. Although it has been thought that only voltage-dependent K+ channels promote excitation, Bockenhauer et al. provide evidence that KCNK2, a K+ leak channel, can be converted into a voltage-dependent channel through posttranslational modification. The authors identified a single consensus cyclic AMP-dependent protein kinase (PKA) phosphorylation motif in KCNK2 at Ser348. Treatment of KCNK2 (in inside-out membrane preparations) with PKA led to decreased channel activity, whereas subsequent treatment with alkaline phosphatase restored KCNK2 activation. Similarly, phosphatase-treated channels stayed open over a wide range of voltages, suggesting that KCNK2 had adopted its leaky voltage-independent state. Treatment of KCNK2 with PKA caused KCNK2 to only be open in depolarizing conditions, possibly indicating that KCNK2 had switched to voltage-dependent channel activity. A KCNK2 Ser348 Ala348 mutant, mimicked the nonphosphorylated wild-type KCNK2 channel, whereas a Ser348 Asp348 mutant, where the aspartate residue approximates a phosphorylated serine residue, functioned in a voltage-dependent manner similar to PKA-treated KCNK2. Thus, these data suggest that KCNK2 can interconvert between voltage-dependent and -independent states and provide neurons with another mechanism to control their excitability. Maylie and Adelman, in an accompanying News & Views, discuss a possible mechanism by which KCNK2 switches states.
D. Bockenhauer, N. Zilberberg, S. A. N. Goldstein, KCNK2: Reversible conversion of a hippocampal potassium leak channel into a voltage-dependent channel. Nature Neurosci. 4, 486-491 (2001). [Online Journal]
J. Maylie, J. P. Adelman, Beam me up, Scottie! TREK channels swing both ways. Nature Neurosci. 4, 457-458 (2001). [Online Journal]
Citation: KCNK2 Is Both Dependent and Independent. Sci. STKE 2001, tw2 (2001).
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882