MFaN is a potent and specific positive allosteric modulator (PAM) of proton-gated proton channel Otop1, dose-dependently potentiates mOtop1 currents with EC50 of 10.3 uM (pH 5.5).
MFaN has equivalent potency and efficacy in potentiating mOtop1 currents under condition of the same pH.
MFaN is inactive on the Otop2 and Otop3 channels from mouse origin (mOtop2 and mOtop3).
MFaN also has no effect to weak inhibition at 10 uM against a panel ion channels including NaV and Kv channels.
Increasing the pH to 6.0 markedly enhanced the efficacy of MFaN in potentiating mOtop1 currents, without affecting its apparent potency.
MFaN does not affect mOtop1 activity at either alkaline nor neutral pH, suggesting that it selectively acts on the acid gating of the mOtop1 channel.
MFaN (10 μM) increases pHi changes in response to acidic stimuli (pH 6.0/5.0) on the influx and efflux of protons mediated by mOTOP1 channels in HEK293 cells.
MFaN enhances cytosal acidification by acting on the Otop1 channel.