Defining the ionic mechanisms of optogenetic control of vascular tone by channelrhodopsin-2.

British Journal of Pharmacology
Nils J G RorsmanPaolo Tammaro

Abstract

Optogenetic control of electromechanical coupling in vascular smooth muscle cells (VSMCs) is emerging as a powerful research tool with potential applications in drug discovery and therapeutics. However, the precise ionic mechanisms involved in this control remain unclear. Cell imaging, patch-clamp electrophysiology and muscle tension recordings were used to define these mechanisms over a wide range of light stimulations. Transgenic mice expressing a channelrhodopsin-2 variant [ChR2(H134R)] selectively in VSMCs were generated. Isolated VSMCs obtained from these mice demonstrated blue light-induced depolarizing whole-cell currents. Fine control of artery tone was attained by varying the intensity of the light stimulus. This arterial response was sufficient to overcome the endogenous, melanopsin-mediated, light-evoked, arterial relaxation observed in the presence of contractile agonists. Ca2+ entry through voltage-gated Ca2+ channels, and opening of plasmalemmal depolarizing channels (TMEM16A and TRPM) and intracellular IP3 receptors were involved in the ChR2(H134R)-dependent arterial response to blue light at intensities lower than ~0.1 mW·mm-2 . Light stimuli of greater intensity evoked a significant Ca2+ influx directly through...Continue Reading

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Citations

Aug 12, 2018·Acta Neuropathologica·Jinping ChengDavid Attwell
Dec 20, 2020·Nature Reviews. Cardiology·Emilia Entcheva, Matthew W Kay
Feb 20, 2021·Nature Neuroscience·David A HartmannAndy Y Shih

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