Here we identify a novel class of biological membrane ion channel blockers called single-walled carbon nanotubes (SWNTs). SWNTs with diameter distributions peaked at ϳ0.9 and 1.3 nm, C 60 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.Because of the physiological role they play, ion channels exhibit unique structures, including the pore that provides the physical pathway for ion movements across the plasma membrane and several charged domains that attract and/or repel ions (1). These characteristics make ion channels easy targets for external agents such as natural toxins and synthetic drugs that react with them by establishing electrochemical interactions. Thus, blocking agents have been used not only as the basic components for commercial pesticides and potential therapeutic drugs but also to infer functional information (1).The identification of new classes of molecules to target ionchannels is of significant interest in biological research, and, therefore, we sought to explore the possibility of using novel materials such as selected single-walled carbon nanotubes (SWNTs), 1 as ion channel blockers. In recent years there have been several attempts to use nanotubes for biological purposes because of their unique mechanical, chemical, and electrical properties (2). For example, nanotubes have been successfully used for the helical crystallization of proteins (3) and the growth of embryonic rat brain neurons (4) and as potential biosensors and bioreactors (5, 6). Here we show that SWNTs of certain diameters can efficiently block K ϩ channels.
MATERIALS AND METHODSNanotubes and Fullerene Synthesis-SWNTs, with a diameter distribution peaked in the 0.8 -0.9 nm range, were grown by chemical vapor deposition (CVD) in a horizontal tube reactor using a three-stage process. In the first stage, the catalyst/support system was obtained via wet mixing followed by combustive calcination. Magnesium nitrate hexahydrate, cobalt nitrate hexahydrate, ammonium heptamolybdate tetrahydrate, and citric acid (the latter to induce combustion) were mixed with enough distilled water to give a clear solution, which was heated to 550°C for 5-10 min in air. The resulting powder of general composition MgO (1-x-y) Co x Mo y (where nanoscale Co-Mo is the catalyst in a typical molybdenum/cobalt atomic ratio of 1:4, and MgO is the catalyst support) was taken out,...