TY - JOUR
T1 - Zn2+ activates large conductance Ca2+-activated K+ channel via an intracellular domain
AU - Hou, Shangwei
AU - Vigeland, Leif E.
AU - Zhang, Guangping
AU - Xu, Rong
AU - Li, Min
AU - Heinemann, Stefan H.
AU - Hoshi, Toshinori
PY - 2010/2/26
Y1 - 2010/2/26
N2 - Zinc is an essential trace element and plays crucial roles in normal development, often as an integral structural component of transcription factors and enzymes. Recent evidence suggests that intracellular Zn2+ functions as a signaling molecule, mediating a variety of important physiological phenomena. However, the immediate effectors of intracellular Zn2+ signaling are not well known. We show here that intracellular Zn2+ potently and reversibly activates large-conductance voltage- and Ca2+-activated Slo1 K+ (BK) channels. The full effect of Zn2+ requires His365 in the RCK1 (regulator of conductance for K+) domain of the channel. Furthermore, mutation of two nearby acidic residues, Asp367 and Glu399, also reduced activation of the channel by Zn2+, suggesting a possible structural arrangement for Zn2+ binding by the aforementioned residues. Extracellular Zn2+ activated Slo1 BK channels when coexpressed with Zn2+-permeable TRPM7 (transient receptor potential melastatin 7) channels. The results thus demonstrate that Slo1 BK channels represent a positive and direct effector of Zn2+ signaling and may participate in sculpting cellular response to an increase in intracellular Zn2+ concentration.
AB - Zinc is an essential trace element and plays crucial roles in normal development, often as an integral structural component of transcription factors and enzymes. Recent evidence suggests that intracellular Zn2+ functions as a signaling molecule, mediating a variety of important physiological phenomena. However, the immediate effectors of intracellular Zn2+ signaling are not well known. We show here that intracellular Zn2+ potently and reversibly activates large-conductance voltage- and Ca2+-activated Slo1 K+ (BK) channels. The full effect of Zn2+ requires His365 in the RCK1 (regulator of conductance for K+) domain of the channel. Furthermore, mutation of two nearby acidic residues, Asp367 and Glu399, also reduced activation of the channel by Zn2+, suggesting a possible structural arrangement for Zn2+ binding by the aforementioned residues. Extracellular Zn2+ activated Slo1 BK channels when coexpressed with Zn2+-permeable TRPM7 (transient receptor potential melastatin 7) channels. The results thus demonstrate that Slo1 BK channels represent a positive and direct effector of Zn2+ signaling and may participate in sculpting cellular response to an increase in intracellular Zn2+ concentration.
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U2 - 10.1074/jbc.M109.069211
DO - 10.1074/jbc.M109.069211
M3 - Article
C2 - 20037152
AN - SCOPUS:77949890953
SN - 0021-9258
VL - 285
SP - 6434
EP - 6442
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 9
ER -