The acid-sensitive ion channels (ASICs) are a family of voltage-insensitive sodium channels activated by external protons. A previous study proposed that the mechanism underlying activation of ASIC consists of the removal of a Ca2+ ion from the channel pore (Immke and McCleskey, 2003). In this work we have revisited this issue by examining single channel recordings of ASIC1 from toadfish (fASIC1). We demonstrate that increases in the concentration of external protons or decreases in the concentration of external Ca2+ activate fASIC1 by progressively opening more channels and by increasing the rate of channel opening. Both maneuvers produced similar effects in channel kinetics, consistent with the former notion that protons displace a Ca2+ ion from a high-affinity binding site. However, we did not observe any of the predictions expected from the release of an open-channel blocker: decrease in the amplitude of the unitary currents, shortening of the mean open time, or a constant delay for the first opening when the concentration of external Ca2+ was decreased. Together, the results favor changes in allosteric conformations rather than unblocking of the pore as the mechanism gating fASIC1. At high concentrations, Ca2+ has an additional effect that consists of voltage-dependent decrease in the amplitude of unitary currents (EC50 of 10 mM at -60 mV and pH 6.0). This phenomenon is consistent with voltage-dependent block of the pore but it occurs at concentrations much higher than those required for gating.
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http://dx.doi.org/10.1085/jgp.200509396 | DOI Listing |
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School of Chemistry and Physics, University of KwaZulu-Natal, Scottsville, South Africa.
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Department of Chemical Biology, Max Planck Institute for Medical Research, Jahnstraße 29, 69120 Heidelberg, Germany.
Protein interactions play a crucial role in regulating cellular mechanisms, highlighting the need for effective methods to control these processes. In this regard, chemical inducers of proximity (CIPs) offer a promising approach to precisely manipulate protein-protein interactions in live cells and . In this study, we introduce pMandi, a photocaged version of the plant hormone-based CIP mandipropamid (Mandi), which allows the use of light as an external trigger to induce protein proximity in live mammalian cells.
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Anhui University of Chinese Medicine, Hefei, 230012, China.
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View Article and Find Full Text PDFACS Omega
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Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan.
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