Archives of Pharmacal Research

  • 제29권4호
  • /
  • Pages.310-317
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  • 2006
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  • 0253-6269(pISSN)
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  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

Chemical Modification of the Human Ether-a-go-go-related gene (HERG) $K^+$ Current by the Amino-Group Reagent Trinitrobenzene Sulfonic Acid

  • Jo Su-Hyun (Department of Physiology, College of Medicine, Cheju National University, Department of Life Science, Pohang University of Science and Technology) ;
  • Choi Se-Young (Department of Physiology and Dental Research Institute, College of Dentistry, Seoul National University) ;
  • Yun Ji-Hyun (Department of Microbiology, College of Medicine, Cheju National University) ;
  • Koh Young-Sang (Department of Microbiology, College of Medicine, Cheju National University) ;
  • Ho Won-Kyung (Department of Physiology, College of Medicine, Seoul National University) ;
  • Lee Chin-O. (Department of Life Science, Pohang University of Science and Technology)
  • 발행 : 2006.04.01
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초록

We investigated the effects of trinitrobenzene sulfonic acid (TNBS), an amino-group reagent, on the human ether-a-go-go-related gene (HERG) $K^+$ channels expressed in Xenopus oocytes. TNBS neutralizes the positively charged amino-groups of peptide N-terminal and lysine residues. External application of TNBS at 10 mM for 5 min irreversibly shifted the curves for currents at the end of the pulse and tail currents of HERG to a more negative potential and decreased the maximal amplitude of the $I_{tail}$ curve $(I_{tail,max})$. TNBS had little effect on either the activated current-voltage relationship or the reversal potential of HERG current, indicating that TNBS did not change ion selectivity properties. TNBS shifted the time constant curves of both activation and deactivation of the HERG current to a more hyperpolarized potential; TNBS's effect was greater on channel opening than channel closing. External $H^+$ is known to inhibit HERG current by shifting $V_{1/2}$ to the right and decreasing $I_{tail,max}$. TNBS enhanced the blockade of external $H^+$ by exaggerating the effect of $H^+$ on $I_{tail,max}$, not on $V_{1/2}$. Our data provide evidence for the presence of essential amino-groups that are associated with the normal functioning of the HERG channel and evidence that these groups modify the blocking effect of external $H^+$ on the current.

키워드

참고문헌

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