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J. Biol. Chem., Vol. 278, Issue 50, 50212-50216, December 12, 2003

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Single-walled Carbon Nanotubes Are a New Class of Ion Channel Blockers^*

Ki Ho Park, Manish Chhowalla¶, Zafar Iqbal||, and Federico Sesti**

From the Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, the Department of Ceramic and Materials Engineering, Rutgers University, Piscataway, New Jersey 08854, and the ^||Department of Chemistry and Environmental Science, New Jersey Institute of Technology University Heights, Newark, New Jersey 07102

Here we identify a novel class of biological membrane ion channel blockers called single-walled carbon nanotubes (SWNTs). SWNTs with diameter distributions peaked at 0.9 and 1.3 nm, C₆₀ fullerenes, multi wall nanotubes (MWNTs), and hyperfullerenes (nano-"onions") were synthesized by several techniques and applied to diverse channel types heterologously expressed in mammalian cells. External as-fabricated and purified SWNTs blocked K⁺ channel subunits in a dose-dependent manner. Blockage was dependent on the shape and dimensions of the nanoparticles used and did not require any electrochemical interaction. SWNTs were more effective than the spherical fullerenes and, for both, diameter was the determining factor. These findings postulate new uses for SWNTs in biological applications and provide unexpected insights into the current view of mechanisms governing the interaction of ion channels with blocking molecules.

Received for publication, September 15, 2003 , and in revised form, September 30, 2003.

^* This work was supported in part by National Institutes of Health Grant R01GM68581-01 (to F. S.).The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence may be addressed: Rutgers University, Ceramic and Materials Engineering, 607 Taylor Rd., Piscataway, NJ 08854. Tel.: 732-445-5619; Fax: 732-445-3258; E-mail: manish1{at}rci.rutgers.edu. **To whom correspondence may be addressed: University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Dept. of Physiology and Biophysics, 675 Hoes Lane, Piscataway, NJ 08854. Tel.: 732-235-4032; Fax: 732-235-5038; E-mail: SESTIFE{at}UMDNJ.EDU.

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