Optogenetic manipulation of cardiac electrical dynamics using sub-threshold illumination: dissecting the role of cardiac alternans in terminating rapid rhythms

• DOI: 10.1007/s00395-022-00933-8
• Publication Date: 2022-04-29T18:07:56Z
• Authors: V. Biasci; L. Santini; G. A. Marchal; S. Hussaini; C. Ferrantini; R. Coppini; L. M. Loew; S. Luther; M. Campione; C. Poggesi; F. S. Pavone; E. Cerbai; G. Bub; L. Sacconi
• Keywords: Heart Rhythm; Normalization property; Dynamics

Cardiac action potential (AP) shape and propagation are regulated by several key dynamic factors such as ion channel recovery intracellular Ca2+ cycling. Experimental methods for manipulating AP electrical dynamics commonly use inhibitors that lack spatial temporal specificity. In this work, we propose an approach based on optogenetics to manipulate cardiac activity employing a light-modulated depolarizing current with intensities too low elicit APs (sub-threshold illumination), but sufficient fine-tune dynamics. We investigated the effects of sub-threshold illumination in isolated cardiomyocytes whole hearts using transgenic mice constitutively expressing light-gated (channelrhodopsin-2, ChR2). find ChR2-mediated prolongs reduces conduction velocity (CV) space-selective reversible manner. Sub-threshold manipulation also affects activity, increasing magnitude alternans. used optical system uses real-time feedback control generate re-entrant circuits user-defined cycle lengths explore role alternans spontaneous termination ventricular tachycardias (VTs). demonstrate VT stability significantly decreases during primarily due increase amplitude oscillations, which implies may be beneficial context self-termination VT.