Peripheral and central employment of acid-sensing ion channels during early bilaterian evolution

Abstract

Acid-sensing ion channels (ASICs) are membrane proteins that endow vertebrate neurons with fast excitatory responses to decreases in extracellular pH. Although previous studies suggest that ASICs are found in certain invertebrates, the lineage in which ASICs emerged and the functional role of ASICs beyond the vertebrates is unknown. We reconstructed ASIC evolution by surveying metazoan ASICs and performing a phylogenetic analysis, which suggests that ASICs evolved in an early bilaterian. This was supported by electrophysiological measurements of proton-gated currents at heterologous channels from diverse bilaterians. This also revealed substantial variation in biophysical properties of broadly related ASICs, with selective sodium/potassium ion permeability ranging from 3- to 36-fold and half-maximal activating pH from 4.2 to 8.1. Furthermore, we studied the expression of ASICs in species outside the vertebrates and found expression in the central nervous system of certain bilaterian lineages but in the periphery, including nervous system, digestive system, and motile ciliated epithelia, of most lineages. The loss of such epithelial cells in Ecdysozoa might explain the loss of ASICs from this major animal lineage. Our results suggest that ASICs emerged in an early bilaterian, and expression in the central nervous system was accompanied or even pre-dated by expression in the periphery.

Comparative analysis defines a broader FMRFamide-gated sodium channel family and determinants of neuropeptide sensitivity

“…S1 ). ASICs are found in numerous bilaterians, including annelids, but are best described in mammals ( 27 ). Mammalian ASICs are closed at pH ≥7.4 and transiently activated by, for example, pH 5, but if resting channels are exposed to very small drops in pH, for example to pH 7, they enter a desensitized state and subsequently pH 5 activates little, if any, current ( Fig.…”

Functional analysis in a model sea anemone reveals phylogenetic complexity and a role in cnidocyte discharge of DEG/ENaC ion channels

“…While ENaC evolved early in vertebrates and might have aided in the osmoregulatory adaption during the transition of vertebrates to land (12), proton-sensitive ASICs are also present in non-vertebrate deuterostomes and some protostomes and likely evolved before the Cambrian explosion (13,14).…”

“…It is found in the epithelial cells of the bile ducts, but its physiological function remains uncertain ( 11 ). While ENaC evolved early in vertebrates and might have aided in the osmoregulatory adaption during the transition of vertebrates to land ( 12 ), proton-sensitive ASICs are also present in non-vertebrate deuterostomes and some protostomes and likely evolved before the Cambrian explosion ( 13, 14 ). Therefore, it has been proposed that ENaC evolved from the ASIC lineage ( 12, 13 ).…”

Comparative analysis defines a broader FMRFamide-gated sodium channel family and determinants of neuropeptide sensitivity

“…S1). ASICs are found in numerous bilaterians, including annelids, but are best described in mammals (25). Mammalian ASICs are closed at pH ≥ 7.4 and transiently activated by e.g.…”