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Published July 27, 2000 | Supplemental Material
Journal Article Open

State-dependent cross-inhibition between transmitter-gated cation channels

Abstract

Transmitter-gated cation channels are detectors of excitatory chemical signals at synapses in the nervous system. Here we show that structurally distinct α3β4 nicotinic and P2X_2 channels influence each other when co-activated. The activation of one channel type affects distinct kinetic and conductance states of the other, and co-activation results in non-additive responses owing to inhibition of both channel types. State-dependent inhibition of nicotinic channels is revealed most clearly with mutant P2X_2 channels, and inhibition is decreased at lower densities of channel expression. In synaptically coupled myenteric neurons, nicotinic fast excitatory postsynaptic currents are occluded during activation of endogenously co-expressed P2X channels. Our data provide a molecular basis and a synaptic context for cross-inhibition between transmitter-gated channels.

Additional Information

© 2000 Macmillan Magazines Ltd. Received 12 April; accepted 26 May 2000. Thanks to H. Li for assistance with preparation of oocytes, and to other members of the group for comments. A Wellcome Trust (UK) International Prize Travelling Fellowship (to B.S.K.) and the NIH supported this work.

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August 19, 2023
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