Zinc activates TREK-2 potassium channel activity.
TWIK-related K(+) channel (TREK)-2 is thought to contribute to setting the resting membrane potential and to tuning action potential properties. In the present study, the effects of divalent metal ions (Ba(2+), Co(2+), Ni(2+), Pb(2+), and Zn(2+)) were examined on TREK-2 expressed in Xenopus oocytes using the two-electrode voltage clamping technique. Pb(2+) inhibited TREK channel activity (IC(50) = 15.6 microM), whereas Zn(2+) enhanced it in a dose-dependent manner (EC(50) = 87.1 microM). Ba(2+) slightly inhibited TREK currents but only at high concentrations. Co(2+) and Ni(2+) had no significant effect. The structural element(s) contributing to the zinc enhancement effect were studied using a series of chimeras consisting of Zn(2+)-activated TREK-2 and Zn(2+)-inhibited TWIK-related acid-sensing K(+) channel-3. The structural elements were localized to the first pore and the preceding extracellular loop of TREK-2, in which multiple residues, including His121, His156, Asp158, and Asn177, are likely to be involved in the zinc activation effect. Stimulation by Zn(2+) may be used as a criterion of TREK-2, distinguishing it from other two-pore K(+) channels.
Kim
Jin-Sung
JS
Department of Life Science, Sogang University, Mapo-Gu, Sinsu-Dong 1, Seoul 121-742, Korea.
Park
Jin-Yong
JY
Kang
Ho-Won
HW
Lee
Eun-Jung
EJ
Bang
Hyoweon
H
Lee
Jung-Ha
JH
D000595:Amino Acid Sequence; D000818:Animals; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007854:Lead / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008670:Metals / Q000494:pharmacology; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists* / Q000737:chemistry / Q000235:genetics; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000187:drug effects; D013268:Stimulation, Chemical; D014981:Xenopus; D015032:Zinc / Q000494:pharmacology*
D018076:DNA, Complementary; C503438:KCNK10 protein, human; C498655:KCNK9 protein, human; C503444:Kcnk10 protein, rat; D008670:Metals; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D011993:Recombinant Fusion Proteins; D007854:Lead; D015032:Zinc