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Subunit‐specific inhibition of acid sensing ion channels by stomatin‐like protein 1
Author(s) -
Kozlenkov Alexey,
Lapatsina Liudmila,
Lewin Gary R.,
Smith Ewan St. John
Publication year - 2014
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2013.258657
Subject(s) - acid sensing ion channel , ion channel , dorsal root ganglion , microbiology and biotechnology , biology , patch clamp , mutant , chemistry , biochemistry , gene , receptor , anatomy , dorsum
Key points Stomatin‐like protein 1 (STOML1) was found both at the plasma membrane and associated with vesicles in the neurites of dorsal root ganglia (DRG) neurones. We found that STOML1 modulates ASIC1a and ASIC3. In the presence of STOML1 acid gated currents carried by ASIC1a were decreased and ASIC3 currents showed accelerated inactivation; STOML1 had no effects on other ASICs. Among the stomatin family, only STOML1 has a sterol carrier protein‐2 domain and removal of this domain prevented inhibition of ASIC1a currents. We generated a mouse with a β ‐galactosidase‐neomycin cassette gene‐trap reporter driven from the STOML1 gene locus to demonstrate that STOML1 is expressed by approximately half of all DRG neurones. Whole‐cell electrophysiology recordings from DRG neurones from STOML1 null mutant mice showed on average larger proton‐gated currents compared to neurones from wild‐type mice.Abstract There are five mammalian stomatin‐domain genes, all of which encode peripheral membrane proteins that can modulate ion channel function. Here we examined the ability of stomatin‐like protein 1 (STOML1) to modulate the proton‐sensitive members of the acid‐sensing ion channel (ASIC) family. STOML1 profoundly inhibits ASIC1a, but has no effect on the splice variant ASIC1b. The inactivation time constant of ASIC3 is also accelerated by STOML1. We examined STOML1 null mutant mice with a β ‐galactosidase‐neomycin cassette gene‐trap reporter driven from the STOML1 gene locus, which indicated that STOML1 is expressed in at least 50% of dorsal root ganglion (DRG) neurones. Patch clamp recordings from mouse DRG neurones identified a trend for larger proton‐gated currents in neurones lacking STOML1, which was due to a contribution of effects upon both transient and sustained currents, at different pH, a finding consistent with an endogenous inhibitory function for STOML1.