Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Neuroscience

Supervisor

Marco Prado

Abstract

Recent studies have shown that murine cardiomyocytes possess a functional intrinsic cholinergic system that can synthesize and release acetylcholine (ACh). The way by which ACh release is regulated however, is not fully understood. Classically, ACh released from neuronal sources is regulated by the vesicular ACh transporter (VAChT). We tested the hypothesis that ACh released from neonatal murine cardiomyocytes is regulated via the VAChT by pharmacologically inhibiting or genetically removing this transporter selectively from cardiomyocytes. Pharmacological inhibition of the VAChT using vesamicol (VES) revealed a significant reduction in ACh release from cultured cardiomyocytes. Cardiomyocytes from genetically-modified mice where the VAChT was selectively removed revealed similar reductions in ACh release. Similar to its role within nerve terminals, these data suggest that the VAChT serves an essential role in regulating ACh release from cardiomyocytes. These experiments suggest that non-neuronal ACh released from cardiomyocytes may act to amplify the effects of neuronally released ACh.

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