Abstract
Acid-sensing ion channels (ASICs) are formed by diverse combinations of ASIC subunit proteins that exhibit distinct sensitivity, kinetics and permeability. To better understand proton signalling in nociceptors, we characterized the pH-dependent activation, kinetics and Ca2+ permeability of proton activated currents. Whole cell patch recordings were obtained from dorsal root ganglion (DRG) neurons (n= 40) that were acutely dissociated and classified by electrophysiological signature into 6 uniform types (type 3, 5, 6, 7, 8 and 9) of neurons known to express ASICs, but differentially express SP and/or CGRP (Petruska et al., 2000; 2002). Increasing proton concentrations had distinct influences on DRG cells. Non-nociceptive (type 3) and nociceptive groups (type 5, 6, 7, 8, 9) had similar thresholds (pH 6.8) but varied in potency (EC50; type 3 and 5 > 6, 7, 8 and 9; p<.05), and reactive range (type 3 (0.4 pH unit) < type 5, 6, 7, 8, 9 (0.7 to 1.4 pH unit), p<.05). Decay kinetics did not covary with nociceptive function (155.7 ± 22.7 to 1463.2 ± 131.6 msec). Because a portion of ASICs are Ca2+ permeable, ratiometric Ca2+ imaging was examined in peptidergic nociceptors with ASIC1a-like kinetics. Ca2+ permeability was observed in both type 5 and 8 cells (pH 6.0; n=14). Ruthenium red (5 μM) did not block Ca2+ entry. In conclusion, nociceptors and non-nociceptors have distinct proton sensitivity. Ca2+ entry via ASICs may support release of peptides into tissues or promote transmitter release at synapses. Supported by NS39874. [Jpn J Physiol 55 Suppl:S140 (2005)]
