Electrostatic Tuning of Cellular Excitability
2010 (English)In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 98, no 3, 396-403 p.Article in journal (Refereed) Published
Voltage-gated ion channels regulate the electric activity of excitable tissues, such as the heart and brain. Therefore, treatment for conditions of disturbed excitability is often based on drugs that target ion channels. In this study of a voltage-gated K channel, we propose what we believe to be a novel pharmacological mechanism for how to regulate channel activity. Charged lipophilic substances can tune channel opening, and consequently excitability, by an electrostatic interaction with the channels voltage sensors. The direction of the effect depends on the charge of the substance. This was shown by three compounds sharing an arachiclonyl backbone but bearing different charge: arachidonic acid, methyl arachidonate, and arachidonyl amine. Computer simulations of membrane excitability showed that small changes in the voltage dependence of Na and K channels have prominent impact on excitability and the tendency for repetitive firing. For instance, a shift in the voltage dependence of a K channel with -5 or +5 mV corresponds to a threefold increase or decrease in K channel density, respectively. We suggest that electrostatic tuning of ion channel activity constitutes a novel and powerful pharmacological approach with which to affect cellular excitability.
Place, publisher, year, edition, pages
2010. Vol. 98, no 3, 396-403 p.
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-54082DOI: 10.1016/j.bpj.2009.10.026ISI: 000274313200006OAI: oai:DiVA.org:liu-54082DiVA: diva2:298247
Original Publication: Sara Börjesson, Teija Parkkari, Sven Hammarström and Fredrik Elinder, Electrostatic Tuning of Cellular Excitability, 2010, BIOPHYSICAL JOURNAL, (98), 3, 396-403. http://dx.doi.org/10.1016/j.bpj.2009.10.026 Copyright: Elsevier Science B.V., Amsterdam http://www.elsevier.com/2010-02-222010-02-222013-10-15Bibliographically approved