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Regulation of TRPC5 currents by intracellular ATP: Single channel studies |
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| Authors: | Michael Dattilo Nicholas J Penington Keith Williams |
| Institution: | 1. Department of Physiology and Pharmacology, State University of New York, Downstate Health Sciences University, Brooklyn, New York
Program in Neural and Behavioral Science and Robert F. Furchgott, Center for Neural and Behavioral Science, State University of New York, Downstate Health Sciences University, Brooklyn, New York;2. Department of Physiology and Pharmacology, State University of New York, Downstate Health Sciences University, Brooklyn, New York |
| Abstract: | TRPC5 channels are nonselective cation channels activated by G-protein-coupled receptors. It was previously found that recombinant TRPC5 currents are inhibited by intracellular ATP, when studied by whole-cell patch-clamp recording. In the present study, we investigated the mechanism of ATP inhibition at the single-channel level using patches from HEK-293 cells transiently transfected with TRPC5 and the M1 muscarinic receptor. In inside-out patches, application of ATP to the intracellular face of the membrane reduced TRPC5 channel activity at both positive and negative potentials without affecting the unitary current amplitude or open dwell time of the channel. The effect of ATP was rapidly reversible. These results suggest that ATP may bind to the channel protein and affect the ability of the channel to open or to remain in an open, nondesensitized state. The activity of TRPC5 channels may be influenced by cellular metabolism via changes in ATP levels. |
| Keywords: | ATP carbachol HEK293 single channels TRPC5 channels |