Sudden Heart Rate Reduction Upon Optogenetic Release of Acetylcholine From Cardiac Parasympathetic Neurons in Perfused Hearts

Frontiers in Physiology
Angel MorenoMatthew W Kay

Abstract

The balance of sympathetic and parasympathetic tone provides exquisite control of heart rate and contractility and has also been shown to modulate coronary flow and inflammation. Understanding how autonomic balance is altered by cardiac disease is an active area of research, and developing new ways to control this balance provides insights into disease therapies. However, achieving acute neuron-specific stimulation of autonomic neurons can be difficult in experiments that measure the acute effects of nerve stimulation on the heart. Conventional electrical and pharmacological approaches can be spatially and temporally non-selective. Cell-specific expression of light-activated channels (channelrhodopsin, ChR2) is a powerful approach that enables control of the timing and distribution of cellular stimulation using light. We present such an optogenetic approach where parasympathetic cardiac neurons are selectively photoactivated at high temporal precision to initiate cholinergic-mediated slowing of heart rate. Mice were crossbred to express ChR2 in peripheral cholinergic neurons using Cre-Lox recombination driven by a choline acetyltransferase (ChAT) promoter. Hearts from adult mice were excised, perfused, and the epicardium was il...Continue Reading

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Citations

Jun 6, 2019·Methods and Protocols·Tania ZagliaMarco Mongillo
Oct 2, 2019·Frontiers in Physiology·Emily A FerencziChristopher L-H Huang
Aug 4, 2020·Royal Society Open Science·Charalampos SigalasRebecca A B Burton
Oct 10, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Jhansi Dyavanapalli
Dec 20, 2020·Nature Reviews. Cardiology·Emilia Entcheva, Matthew W Kay
Jan 9, 2021·Frontiers in Physiology·Joseph Hadaya, Jeffrey L Ardell
Apr 23, 2021·Acta Physiologica·Gisele L CavalcanteJoão Paulo J Sabino
Sep 21, 2021·Frontiers in Physiology·Balázs ÖrdögDaniël A Pijnappels

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Methods Mentioned

BETA
dissections
fluorescence imaging
chip
fluorescence microscopy

Software Mentioned

SPSS
MATLAB

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