RT Journal Article
SR Electronic
T1 Zinc Activates TREK-2 Potassium Channel Activity
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 618
OP 625
DO 10.1124/jpet.105.084418
VO 314
IS 2
A1 Jin-Sung Kim
A1 Jin-Yong Park
A1 Ho-Won Kang
A1 Eun-Jung Lee
A1 Hyoweon Bang
A1 Jung-Ha Lee
YR 2005
UL http://jpet.aspetjournals.org/content/314/2/618.abstract
AB 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 (Ba2+, Co2+, Ni2+, Pb2+, and Zn2+) were examined on TREK-2 expressed in Xenopus oocytes using the two-electrode voltage clamping technique. Pb2+ inhibited TREK channel activity (IC50 = 15.6 μM), whereas Zn2+ enhanced it in a dose-dependent manner (EC50 = 87.1 μM). Ba2+ slightly inhibited TREK currents but only at high concentrations. Co2+ and Ni2+ had no significant effect. The structural element(s) contributing to the zinc enhancement effect were studied using a series of chimeras consisting of Zn2+-activated TREK-2 and Zn2+-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 Zn2+ may be used as a criterion of TREK-2, distinguishing it from other two-pore K+ channels. The American Society for Pharmacology and Experimental Therapeutics