Physiological and Pharmacological Characteristics of Native Proton-Activated Ion Channels

Abstract

Proton-activated ion channels (ASICs) are widely distributed in the CNS and take part in many physiological processes. We report here studies characterizing pH-induced currents in various neuron types. Overall, the data provide evidence that currents in all these neurons are mediated mainly by heterodimeric ASICs; interneurons in the striatum radiatum of the hippocampus, pyramidal neurons in layer 2 of the medial prefrontal cortex, and interneurons in the striatum have receptors with weak pH sensitivity and pharmacological profiles combining the features of both ASIC1a and ASIC2a subunits. Pyramidal cells in layer 3 of the medial prefrontal cortex also have the same pharmacological profile but greater sensitivity to protons. In cerebellar Purkinje cells, heteromeric receptors are formed mainly from ASIC1a and ASIC2b subunits, as there is no sensitivity to ASIC2a-specific ligands though currents are induced by weak acidification.