The endogenous cardiac cholinergic system: a robust and independent regulator of ventricular conduction

Le résumé fourni par la source

This commentary refers to ‘An endogenous cholinergic system controls electrical conduction in the heart’, by D. Xie et al, https://doi.org/10.1093/eurheartj/ehae699 and ‘Another pathophysiological feature of the impairment of the non-neuronal cardiac cholinergic system that leads to arrhythmogenesis’, by Y. Kakinuma, https://doi.org/10.1093/eurheartj/ehaf1108. We thank Dr. Yoshihiko Kakinuma for his thoughtful commentary on our recent work.1 His expertise in the non-neuronal cardiac cholinergic system (NNCCS) is well recognized, and we appreciate this opportunity to address his three main points. Regarding the use of 100 µM acetylcholine (ACh) in our patch-clamp studies, the local ACh concentration in the cardiomyocyte microenvironment remains unknown. In non-neuronal cholinergic systems, ACh can accumulate in confined intercellular spaces, reaching concentrations far exceeding typical synaptic levels.2 Higher ACh concentrations are often methodologically necessary in patch-clamp studies of non-neuronal tissues to elicit reproducible currents owing to diffuse, non-synaptic transmitter release.3–5 Our dose-response experiments showed a clear concentration-dependent effect, and the consistent use of 100 µM ACh across antagonist tests ensured internal validity. The abolition of currents by mecamylamine and α-bungarotoxin, but not atropine, strongly supports the specificity of nicotinic ACh receptors (nAChRs) in this response.

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