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The sequence of the hydrophobic "P" (pore) region of a K(+)-selective channel from the kidney (ROMK2) was altered to match that of the closely related inward rectifier (IRK1) channel by changing two amino acids, leucine (L) 117 and valine (V) 121, to isoleucine (I) and threonine (T), respectively. The mutant channel expressed in Xenopus laevis oocytes had an apparent inhibition constant at zero voltage [Ki(0)] in the presence of Ba2+ of 0.07 +/- 0.01 mM, which was more than 50 times lower than the Ki(0) of the wild-type channel (4.7 +/- 1.0 mM). The increased sensitivity to Ba2+ was accounted for by the point mutation V121T. Single-channel measurements indicated that the increased affinity involved an increase in the on-rate for Ba2+ block and a decrease in the off-rate. Block by Ca+ was also enhanced. The single-channel conductance of the L1171/ V121T mutant was increased by 50%, whereas the degree of inward rectification, ion selectivity, and apparent affinity for K+ were essentially unchanged. When the neutral asparagine residue within the second putative membrane-spanning domain of the ROMK channel was substituted with aspartic acid, the corresponding amino acid in IRK1, the degree of inward rectification was enhanced but Ba2+ block and single-channel inward conductance were unaffected. Thus the site of Ba2+ binding appears to be distinct from the locus of internal Mg2+ block and from at least one of the sites that determines K+ conjuctivity.

We report on the development of a sensitive high frequency susceptometer capable of measuring in the frequency range from 25 kHz up to 10 MHz with a volume susceptibility sensitivity of 3.5 × 10 -5 at 100 kHz corresponding to about 0.3 % of the measured AC susceptibility. In combination with the previous reported DynoMag system capable of measuring dynamic magnetic properties in the range from 1 Hz to 200 kHz we are thus able to measure dynamic magnetic properties between 1 Hz to 10 MHz with high magnetic sensitivity. We will show AC susceptometry applications and results within the fields of magnetic hyperthermia and dynamic magnetic characterization of magnetic nanoparticle system with different particle sizes and magnetic properties.

The magnetic guidance of antiplastic and antibacterial agents as well as x-ray and MRI contrast substances in vivo by means of magnetic particles has been attempted repeatedly during the last 2 decades with more or less success. When using microparticles, the circulation time in the blood, the biodistribution, and to a greater or lesser extent, the specific targeting are determined by the uniformity of size, chemical composition, surface modification, and the electric surface charge. The electrophoretic mobility is an important parameter for the prediction of the usefulness of the prepared particle, modified by chemical and biological molecules. For its success, radionuclide therapy depends on the critical relationship between the amount of radioactive isotopes in the target tissue and in critical normal tissue. Because the implementation of radioimmunotherapy for the treatment of cancer has proven to be considerably more difficult than initially anticipated, we propose the use of magnetic nanospheres for the well directed delivery of radionuclides to a tumor after the intravenous administration of the biodegradable colloidal suspension.

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