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1 Department of Physiology and Cell Biology, COE Program for Brain Integration and its Disorders, Tokyo Medical and Dental University Graduate School and Faculty of Medicine, Tokyo 113-8519, Japan2 Division of Biophysics and Neurobiology, Department of Molecular Physiology, National Institute for Physiological Sciences, Aichi 444-8585, Japan3 CREST, Japan Science and Technology Corporation, Saitama 332-0012, Japan
Ligand-gated ion channels underlie and play important roles in synaptic transmission, and it is generally accepted that the ion channel pores have a rigid structure that enables strict regulation of ion permeation. One exception is the P2X ATP-gated channel. After application of ATP, the ion selectivity of the P2X2 channel time-dependently changes, i.e. permeability to large cations gradually increases, and there is significant cell-to-cell variation in the intensity of inward rectification. Here we show P2X2 channel properties are correlated with the expression level: increasing P2X2 expression level in oocytes increases permeability to large cations, decreases inward rectification and increases ligand sensitivity. We also observed that the inward rectification changed in a dose-dependent manner, i.e. when low concentration of ATP was applied to an oocyte with a high expression level, the intensity of inward rectification of the evoked current was weak. Taken together, these results show that the pore properties of P2X2 channel are not static but change dynamically depending on the open channel density. Furthermore, we identified by mutagenesis study that Ile328 located at the outer mouth of the pore is critical for the density-dependent changes of P2X2. Our findings suggest synaptic transmission can be modulated by the local density-dependent changes of channel properties caused, for example, by the presence of clustering molecules.
(Received 15 March 2004;
accepted after revision 20 April 2004;
first published online 23 April 2004)
Corresponding author Y. Kubo: Division of Biophysics and Neurobiology, Department of Molecular Physiology, National Institute for Physiological Sciences, Aichi 444-8585, Japan. Email: ykubo{at}nips.ac.jp
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