Expression Level Dependence of the Gating and Permeation Properties of P2X Receptor Channels

Abstract

P2X receptors are cation channels that are activated by extracellular ATP, and that are widely expressed in virtually every tissue. Seven subtypes of P2X receptors have been identified in mammals, and they play important roles in sensory signaling and inflammation. The expression levels of P2X receptors have been reported to change in response to various stimuli. For instance, the expression level of P2X4 receptors increased strikingly in microglia of spinal cord after nerve injury, and these receptors were suggested to play important roles for tactile allodynia1. Interestingly, it has also been reported that both gating and permeation properties of some P2X receptors change in a channel-density dependent manner2,3. Here we transfected P2X2 receptor channels into HEK293 cells with either high or low expression vectors, and then studied the properties of these channels at varying expression levels. Our results suggest that the selectivity, rectification and ATP sensitivity of P2X receptor channels exhibit expression level dependence, as if distinct open states predominate at different expression levels. These changes do not appear to result from artefactual changes in intracellular ion concentrations or voltage errors, and we are currently studying the underlying mechanism.