Measurement of state-dependent action of sodium channel inhibitors
-
1
Pharmacology and Drug Safety Research, Gedeon Richter Plc., Hungary
Sodium channels are involved in normal cardiac, muscular, and neural functions, but their abnormally increased activity may lead to pathological states, like epilepsy, chronic pain, or psychiatric disorders. Sodium channel blocking drugs have a clinically advantageous feature, namely, they preferentially block sodium channels of over-active neurons involved in pathological processes, while leaving normal physiological functions relatively intact. An ideal sodium channel blocker has much higher affinity to the inactivated than the resting conformation of the sodium channel protein. Recently emerged automated patch-clamp techniques offer a reliable way of testing this state-dependency with sufficient throughput. CHO cells stably expressing sodium channel alpha subunits were investigated by using the QPatch automated patch-clamp system. The holding potential dependence of the available whole-cell currents was determined between -25 and -100 mV at 5 mV steps (10-s conditioning pulses followed by a 10-ms test pulse to 0 mV) at various drug concentrations. V1/2 was defined as the potential where 50% of the channels were inactivated. IC50 for blocking sodium currents obtained at V1/2 was used for characterizing the potency of each compound. Furthermore, IC50 values in the presence of various drug concentrations were calculated using inhibition data extracted from the inactivation curves. After plotting IC50s against holding potential values on a semi-logarithmic scale a linear equation was fitted to the data and the slope factor was used to quantitatively characterize the state dependence of each compound. Preliminary results with reference substances show that this method is suitable for testing sodium channel blockers for state dependency.
Conference:
12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009.
Presentation Type:
Poster Presentation
Topic:
Developmental neurobiology and subcortical functions
Citation:
Kocsis
P,
Fodor
L and
Tarnawa
I
(2009). Measurement of state-dependent action of sodium channel inhibitors.
Front. Syst. Neurosci.
Conference Abstract:
12th Meeting of the Hungarian Neuroscience Society.
doi: 10.3389/conf.neuro.01.2009.04.062
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
02 Mar 2009;
Published Online:
02 Mar 2009.
*
Correspondence:
Pál Kocsis, Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary, p.kocsis@richter.hu