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Tunable Molecular Logic Gates Designed for Imaging Released Neurotransmitters.

Jessica L Klockow¹, Kenneth S Hettie¹, Kristen E Secor¹

¹Department of Chemistry, University of Missouri, 601 S. College Ave. Columbia, MO 65211 (USA).

Chemistry (Weinheim an Der Bergstrasse, Germany)

|June 30, 2015

Summary

New fluorescent molecular logic gates, called ExoSensors, can image neurotransmitters released during exocytosis. These sensors offer a twelvefold fluorescence enhancement for visualizing released neurotransmitters.

Keywords:

chemosensors exocytosis fluorescence molecular logic gates neurotransmitters

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Area of Science:

Molecular imaging
Neuroscience
Chemical biology

Background:

Exocytosis releases neurotransmitters from vesicles.
Current imaging methods have limitations in visualizing released neurotransmitters.
Understanding neurotransmitter release is crucial for neurological research.

Purpose of the Study:

To design and develop novel fluorescent molecular logic gates (ExoSensors) for imaging specific vesicular primary-amine neurotransmitters.
To create sensors that respond to both neurotransmitter binding and pH changes during exocytosis.
To achieve enhanced fluorescence output for direct visualization of exocytosed neurotransmitters.

Main Methods:

ExoSensors were designed using a coumarin-3-aldehyde scaffold.
pH-sensitive functionality was integrated into the fluorophore π-system.
Sulfonamide substituents were used to tune the pKa of the pH-sensitive group.
Fluorescence output was evaluated under conditions mimicking exocytosis.

Main Results:

ExoSensors demonstrated a unique turn-on fluorescence output.
A correlation between pKa and fluorescence output was identified.
A twelvefold fluorescence enhancement was achieved under simulated exocytosis conditions.
ExoSensors specifically visualized neurotransmitters released from secretory vesicles.

Conclusions:

ExoSensors are effective molecular imaging tools for visualizing neurotransmitter release during exocytosis.
The tunable nature of ExoSensors allows for optimization of fluorescence output.
These sensors provide a direct method for studying exocytosis-related neurotransmitter dynamics.