New mechanism for voltage induced charge movement revealed in GPCRs--theory and experiments.

PloS One
Assaf ZoharH Parnas

Abstract

Depolarization induced charge movement associated currents, analogous to gating currents in channels, were recently demonstrated in G-protein coupled receptors (GPCRs), and were found to affect the receptor's Agonist binding Affinity, hence denoted AA-currents. Here we study, employing a combined theoretical-experimental approach, the properties of the AA-currents using the m2-muscarinic receptor (m2R) as a case study. We found that the AA-currents are characterized by a "bump", a distinct rise followed by a slow decline, which appears both in the On and the Off responses. The cumulative features implied a directional behavior of the AA-currents. This forced us to abandon the classical chemical reaction type of models and develop instead a model that includes anisotropic processes, thus producing directionality. This model fitted well the experimental data. Our main findings are that the AA-currents include two components. One is extremely fast, approximately 0.2 ms, at all voltages. The other is slow, 2-3 ms at all voltages. Surprisingly, the slow component includes a process which strongly depends on voltage and can be as fast as 0.3 ms at + 40 mV. The reason that it does not affect the overall time constant of the slow compo...Continue Reading

References

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Citations

Jan 5, 2011·The Journal of Cell Biology·Yonatan M KupchikHanna Parnas
Dec 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Noa DekelFrancisco Bezanilla
May 7, 2013·Endocrine Reviews·Gunnar KleinauHeike Biebermann

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Software Mentioned

PCLAMP8
Matlab

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