Kinetics of P2X₇ receptor-operated single channels currents

¹ Martin-Luther-University Halle, Julius-Bernstein-Institute for Physiology
² University of Kentucky, Dept. of Internal Medicine
³ RWTH Aachen University, Department of Molecular Pharmacology
⁴ Martin Luther University

^* To whom correspondence should be addressed. E-mail: fritz.markwardt{at}medizin.uni-halle.de.

Submitted on June 26, 2006
Revised on August 1, 2006
Accepted on 11 December 2006

	Abstract

Human P2X₇ receptors were expressed in Xenopus laevis oocytes and single channels were recorded using the patch clamp technique in the outside-out configuration. ATP^4- evoked two types of P2X₇ receptor-mediated single channel currents characterized by short and long-lived openings. The short- and long-lasting open states had mean open times of ~5 and ~20 ms and slope conductances near -60 mV of 9 and 13 pS, respectively. The probability of observing long-lasting openings increased with the increasing ATP^4- concentration ([ATP^4-]). The open probabilities of the short and long openings were strongly [ATP^4-]-dependent with EC₅₀ values of ~0.3 mM and ~0.1 mM ATP^4-, respectively. Activation and deactivation of the short openings followed exponential time courses with time constants in the range of 20 ms, and displayed a shallow [ATP^4-] dependence of the activation process. The channel kinetics did not significantly change during sustained P2X₇ receptor activation for several minutes, as was also observed in recordings in the cell-attached patch clamp configuration. The kinetics of the short channel openings at negative membrane potentials fitted well to a linear C-C-C-O model with two ATP^4- binding steps at equal binding sites with a dissociation constant K_d of 139 µM.

Key Words: P2X receptor, kinetics, model, patch clamp, purinergic receptor

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