The effects of (2-hydroxypropyl)- β-cyclodextrin (HPβCD), a cyclic oligomer, on membrane electroporation-induced inward current (IMEP) in pituitary tumor (GH3) cells were experimentally and analytically characterized. Depletion of membrane cholesterol by exposing cells to HPβCD (2 mM) increased the activation time constant of delayed rectifier K+ current. Such maneuver resulted in a significant reduction of IMEP density. 2,2’-Azo-bis(2-amidinopropane) dihydrochloride (AAPH), an initiator of free radicals, increased the magnitude of IMEP. AAPH-stimulated IMEP was not reversed by the blockers of Ca2+-activated K+ channels, but by LaCl3 or MnCl2. However, in HPβCD-treated cells, the ability of AAPH to enhance IMEP was abolished. Under such maneuver, the gating charge of IMEP activation was increased by 2 fold, along with a hyperpolarized shift of the activation curve by 30 mV. No change in single-channel conductance of MEP-induced channels during cell exposure to HPβCD was demonstrated. The energy change of IMEP in untreated and HPβCD-treated cells was estimated to be -17.7 and -44.8 kJ/mol, respectively, and the perturbation of free energy following HPβCD treatment was -27.1 kJ/mol. Based on an MEP model, cell exposure to HPβCD increased the edge energy of the electropore size. By use of a two barrier-one site barrier model, HPβCD treatment can increase both the peak height and well depth of the barrier profile. Taken together, depletion of membrane cholesterol by HPβCD can elevate the edge energy of pore formation, thereby decreasing the IMEP magnitude. The channel-suppressing properties during membrane cholesterol depletion with HPβCD might thus contribute to the underlying mechanisms by which such maneuver alters neuronal or neuroendocrine function.

This content is only available via PDF.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.