Abstract
Acid‐sensing ion channels (ASICs) are cation channels that are activated by protons (H+). They are expressed in neurons throughout the nervous system and may play important roles in several neurologic disorders including inflammation, cerebral ischemia, seizures, neurodegeneration, anxiety, depression, and migraine. ASICs generally produce transient currents that desensitize in response to a decrease in extracellular pH. Under certain conditions, the inactivation of ASICs can be incomplete and allow them to produce sustained currents. Here, we characterize the properties of both transient and sustained acid‐induced currents in cultured mouse dorsal root ganglia (DRG) neurons. At pH levels between 7.3 and 7.1 they include “window currents” through ASICs. With stronger acid signals sustained currents are maintained in the absence of extracellular Na+ or the presence of the ASIC blockers amiloride and Psalmotoxin‐1(PcTx1). These sustained responses may have several different origins in these cells, including acid‐induced stimulation of inward Cl− currents, block of outward K+ currents, and augmentation of inward H+ currents, properties that distinguish these novel sustained currents from the well‐characterized transient currents.
Highlights
The acid-sensing ion channels (ASICs) are cation channels that are activated by protons (H+) and are expressed in neurons throughout the nervous system
Several lines of evidence indicate that ASIC channels are involved in pain pathways in both the peripheral and the central nervous system
Among the different ASIC channels, ASIC1 and ASIC3 display the highest sensitivity to extracellular protons, with activation thresholds just below the physiological pH, around pH 7.0 and pH 7.2, respectively
Summary
The acid-sensing ion channels (ASICs) are cation channels that are activated by protons (H+) and are expressed in neurons throughout the nervous system. ASICs are part of a superfamily of channels that includes the epithelial Na channel (ENaC), FMRFamide-gated channels (FaNaC), and mechanosensitive channels in the MEC/ DEG family (Grunder and Pusch 2015; Kellenberger and Schild 2015). They are weakly voltage-dependent and have a variable selectivity for Na+ over K+ and other cations (Yang and Palmer 2014; Grunder and Pusch 2015).
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