Fast Drug Application

Heckmann, Manfred; Hallermann, Stefan

doi:10.1007/978-1-59745-492-6_9

Cited by 1 publication

(1 citation statement)

References 18 publications

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“…High-velocity piezoelectric translators are currently used to overcome this limitation; however, they often suffer from resonant “ringing” after very brief excursions, which produces unwanted fluidic oscillations (Jonas, 1995; Clements, 1997; Mozrzymas et al, 2007), they require the use of high voltages, which requires electrical shielding to prevent additional noise contributions (Jonas, 1995; Clements, 1997; Heckmann and Pawlu, 2002), and they have a limited range of motion (typically 20–80 μm), which substantially limits the potential complexity of experimental protocols. Thus, if LGICs are to be studied in vitro under physiologically relevant conditions, an alternate approach is needed.…”

Section: Resultsmentioning

confidence: 99%

Achieving synaptically relevant pulses of neurotransmitter using PDMS microfluidics

Botzolakis

Maheshwari

Feng

et al. 2009

Journal of Neuroscience Methods

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Fast synaptic transmission is mediated by post-synaptic ligand-gated ion channels (LGICs) transiently activated by neurotransmitter released from pre-synaptic vesicles. Although disruption of synaptic transmission has been implicated in numerous neurological and psychiatric disorders, effective and practical methods for studying LGICs in vitro under synaptically relevant conditions are unavailable. Here, we describe a novel microfluidic approach to solution switching that allows for precise temporal control over the neurotransmitter transient while substantially increasing experimental throughput, flexibility, reproducibility, and cost-effectiveness. When this system was used to apply ultra-brief (~400 μs) GABA pulses to recombinant GABAA receptors, members of the cys-loop family of LGICs, the resulting currents resembled hippocampal inhibitory post-synaptic currents (IPSCs) and differed from currents evoked by longer, conventional pulses, illustrating the importance of evaluating LGICs on a synaptic timescale. This methodology should therefore allow the effects of disease-causing mutations and allosteric modulators to be evaluated in vitro under physiologically relevant conditions.

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