Intracellular Uncaging of cGMP with Blue Light

Hitesh K. Agarwal; Shenyu Zhai; D. James Surmeier; Graham C.R. Ellis-Davies

doi:10.1021/acschemneuro.7b00237

Intracellular Uncaging of cGMP with Blue Light

Hitesh K. Agarwal, Shenyu Zhai, D. James Surmeier, Graham C.R. Ellis-Davies^*

^*Corresponding author for this work

Neuroscience

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

We have made a new caged cGMP that is photolyzed with blue light. Using our recently developed derivative of 7-diethylaminocourmarin (DEAC) called DEAC450, we synthesized coumarin phosphoester derivatives of cGMP with two negative charges appended to the DEAC450 moiety. DEAC450-cGMP is freely soluble in physiological buffer without the need for any organic cosolvents. With a photolysis quantum yield of 0.18 and an extinction coefficient of 43 000 M^-1 cm^-1 at 453 nm, DEAC450-cGMP is the most photosensitive caged cGMP made to date. In patch-clamped neurons in acutely isolated brain slices, blue light effectively uncaged cGMP from DEAC450 and facilitated activation of hyperpolarization and cyclic nucleotide gated cation (HCN) channels in cholinergic interneurons. Thus, DEAC450-cGMP has a unique set of optical and chemical properties that make it a useful addition to the optical arsenal available to neurobiologists.

Original language	English (US)
Pages (from-to)	2139-2144
Number of pages	6
Journal	ACS Chemical Neuroscience
Volume	8
Issue number	10
DOIs	https://doi.org/10.1021/acschemneuro.7b00237
State	Published - Oct 18 2017

Keywords

Caged compounds
HCN channels
blue light
cGMP
coumarin
neurophysiology

ASJC Scopus subject areas

Biochemistry
Physiology
Cognitive Neuroscience
Cell Biology

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10.1021/acschemneuro.7b00237

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title = "Intracellular Uncaging of cGMP with Blue Light",

abstract = "We have made a new caged cGMP that is photolyzed with blue light. Using our recently developed derivative of 7-diethylaminocourmarin (DEAC) called DEAC450, we synthesized coumarin phosphoester derivatives of cGMP with two negative charges appended to the DEAC450 moiety. DEAC450-cGMP is freely soluble in physiological buffer without the need for any organic cosolvents. With a photolysis quantum yield of 0.18 and an extinction coefficient of 43 000 M-1 cm-1 at 453 nm, DEAC450-cGMP is the most photosensitive caged cGMP made to date. In patch-clamped neurons in acutely isolated brain slices, blue light effectively uncaged cGMP from DEAC450 and facilitated activation of hyperpolarization and cyclic nucleotide gated cation (HCN) channels in cholinergic interneurons. Thus, DEAC450-cGMP has a unique set of optical and chemical properties that make it a useful addition to the optical arsenal available to neurobiologists.",

keywords = "Caged compounds, HCN channels, blue light, cGMP, coumarin, neurophysiology",

author = "Agarwal, {Hitesh K.} and Shenyu Zhai and Surmeier, {D. James} and Ellis-Davies, {Graham C.R.}",

note = "Funding Information: *E-mail: graham.davies@mssm.edu. ORCID Graham C. R. Ellis-Davies: 0000-0003-4179-5455 Present Address §H.K.A.: Pharmaceutical Sciences, School of Pharmacy, South University, Columbia, SC 29203. Author Contributions H.K.A. and S.Z. contributed equally to this work. H.K.A. synthesized DEAC450-cGMP. G.C.R.E.-D. characterized the photochemical properties of DEAC450-cGMP. S.Z. and D.J.S. designed and performed the electrophysiological experiments. S.Z. analyzed the physiology data. All authors commented upon the MS and approved the final submission. Funding This work was supported by the NIH (GM053395 and NS069720 to G.C.R.E.-D., NS34696 to D.J.S.). Notes The authors declare no competing financial interest. Publisher Copyright: {\textcopyright} 2017 American Chemical Society.",

year = "2017",

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doi = "10.1021/acschemneuro.7b00237",

language = "English (US)",

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AU - Agarwal, Hitesh K.

AU - Zhai, Shenyu

AU - Surmeier, D. James

AU - Ellis-Davies, Graham C.R.

N1 - Funding Information: *E-mail: graham.davies@mssm.edu. ORCID Graham C. R. Ellis-Davies: 0000-0003-4179-5455 Present Address §H.K.A.: Pharmaceutical Sciences, School of Pharmacy, South University, Columbia, SC 29203. Author Contributions H.K.A. and S.Z. contributed equally to this work. H.K.A. synthesized DEAC450-cGMP. G.C.R.E.-D. characterized the photochemical properties of DEAC450-cGMP. S.Z. and D.J.S. designed and performed the electrophysiological experiments. S.Z. analyzed the physiology data. All authors commented upon the MS and approved the final submission. Funding This work was supported by the NIH (GM053395 and NS069720 to G.C.R.E.-D., NS34696 to D.J.S.). Notes The authors declare no competing financial interest. Publisher Copyright: © 2017 American Chemical Society.

PY - 2017/10/18

Y1 - 2017/10/18

N2 - We have made a new caged cGMP that is photolyzed with blue light. Using our recently developed derivative of 7-diethylaminocourmarin (DEAC) called DEAC450, we synthesized coumarin phosphoester derivatives of cGMP with two negative charges appended to the DEAC450 moiety. DEAC450-cGMP is freely soluble in physiological buffer without the need for any organic cosolvents. With a photolysis quantum yield of 0.18 and an extinction coefficient of 43 000 M-1 cm-1 at 453 nm, DEAC450-cGMP is the most photosensitive caged cGMP made to date. In patch-clamped neurons in acutely isolated brain slices, blue light effectively uncaged cGMP from DEAC450 and facilitated activation of hyperpolarization and cyclic nucleotide gated cation (HCN) channels in cholinergic interneurons. Thus, DEAC450-cGMP has a unique set of optical and chemical properties that make it a useful addition to the optical arsenal available to neurobiologists.

AB - We have made a new caged cGMP that is photolyzed with blue light. Using our recently developed derivative of 7-diethylaminocourmarin (DEAC) called DEAC450, we synthesized coumarin phosphoester derivatives of cGMP with two negative charges appended to the DEAC450 moiety. DEAC450-cGMP is freely soluble in physiological buffer without the need for any organic cosolvents. With a photolysis quantum yield of 0.18 and an extinction coefficient of 43 000 M-1 cm-1 at 453 nm, DEAC450-cGMP is the most photosensitive caged cGMP made to date. In patch-clamped neurons in acutely isolated brain slices, blue light effectively uncaged cGMP from DEAC450 and facilitated activation of hyperpolarization and cyclic nucleotide gated cation (HCN) channels in cholinergic interneurons. Thus, DEAC450-cGMP has a unique set of optical and chemical properties that make it a useful addition to the optical arsenal available to neurobiologists.

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KW - coumarin

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JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

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ER -

Intracellular Uncaging of cGMP with Blue Light

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