Simultaneous optical and electrical tracking of heart activity

Date:
October 5, 2021
Source:
University of Bern
Summary:
It is still elusive to what extent interactions between different
cell types of the heart influence the normal heart rhythm and
possibly trigger life-threatening arrhythmias. A new measurement
method combines optical and electrical recording of cardiac
ventricular activation which, in conjunction with optogenetics,
will permit finding comprehensive answers to these questions.



FULL STORY ==========================================================================
It is still elusive to what extent interactions between different cell
types of the heart influence the normal heart rhythm and possibly trigger
life- threatening arrhythmias. A new measurement method developed at the University of Bern combines for the first time optical and electrical
recording of cardiac ventricular activation which, in conjunction
with optogenetics, will permit finding comprehensive answers to these questions.


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The normal function of the heart is based on a pacemaker that generates electrical impulses ('action potentials') which spread rapidly throughout
the heart muscle where they trigger the contraction leading to the
heartbeat. In the past, it was assumed that the propagation of action potentials was controlled exclusively by cardiac muscle cells. However,
recent findings suggest that other cell types of the heart, such as
connective tissue cells ('fibroblasts') and macrophages, may additionally affect action potential propagation and, thus, play a significant role
in determining cardiac function.

These findings were obtained using a new method called optogenetics that
uses light to control the electrical behavior of defined cell types like fibroblasts thereby permitting the assessment of their involvement in
the cardiac activation process.

To enable comprehensive optogenetic studies with hearts, researchers
led by Stephan Rohr of the Department of Physiology at the University of
Bern developed a new experimental system called 'Panoramic Opto-Electrical Measurement and Stimulation (POEMS)' system. The POEMS system is the first
to allow simultaneous optical and electrical measurements and stimulation extending over the entire ventricular surface of mouse hearts. Results
obtained with the system are expected to open new perspectives in the
study of normal cardiac function and the investigation of mechanisms
causing cardiac arrhythmias. The study describing the system was published
in the journal Nature Communications.

Connective tissue cells as a cause of cardiac arrhythmias? Cell culture experiments have previously shown that cardiac muscle cells communicate
with activated cardiac fibroblasts by means of electrical signals and
that this interaction leads to cardiac arrhythmias. However, it is still unknown whether this mechanism is also operational in intact hearts
because conventional electrophysiological methods are not suited to
investigate this question.

The lack of suitable experimental approaches is overcome these days
by optogenetics that permits a direct interrogation of the presence
and functional consequences of cellular interactions between muscle and non-muscle cells of the heart. Presence of direct electrical communication
can be assessed by letting specific cell types like fibroblasts express so-called "optogenetic voltage reporters." On the other hand, the
functional consequences of such coupling can be investigated by expressing 'optogenetic voltage actuators' in these cells and by observing the
effects of light-activation on whole heart electrophysiology. Presently, conducting optogenetic experiments is complex and equipment intensive. In addition, it is not possible to combine electrode-based experiments with optical studies, which severely limits the range of possible experiments.

POEMS systemcreates new possibilities "With our POEMSsystem, all of these disadvantages have been overcome, as the entire surface of the ventricles
is covered with a combination of optical and electrical measurement and stimulation sites, which allows free combinations of both modalities,"
explains Professor Stephan Rohr, lead author of the study.

The core of the new POEMSsystem consists of a cup fitting the size of
mouse hearts with its inner surface being lined by 294 optical fibers
and 64 electrodes. All optical fibers and electrodes can be individually configured as measurement and stimulation sites thereby permitting a
precise tailoring of individual experiments to the specific requirements
of the optogenetic reporter and actuator used in a given experiment.

Simultaneous optical and electrical panoramic measurements of cardiac activation using stimulated mouse hearts expressing optogenetic voltage reporters demonstrated that the POEMSsystem provides, irrespective of
the measurement modality, congruent and highly accurate measurements
of ventricular action potential propagation with differences between
optically and electrically determined activation times less than a
millisecond. Going beyond, the POEMS system was designed with the goal
to enable straightforward and efficient experimentation. "With our
'drop&go' approach, experiments can be started immediately after the
isolated mouse is placed in the measurement container," says co-author
of the study Michael Rieger, who developed the system together with
other members of the Department of Physiology. The gentle treatment
of the hearts increasing the success rate of experiments as well as
the increased information content provided by the POEMS system is also
relevant with regards to the 3R principles (replace, reduce, refine)
because the number of animal experiments needed to answer a given question
can be substantially reduced.

"With the POEMSsystem in place, we are presently investigating the burning question of whether cardiac arrhythmias can also be caused by non-muscle
cells such as activated connective tissue cells," says Stephan Rohr. If
this should be the case, it would open up new avenues for the treatment
of cardiac arrhythmias as cell types different from muscle cells may
become targets for anti-arrhythmic therapies.

The study was supported by the Swiss National Science Foundation SNSF.

========================================================================== Story Source: Materials provided by University_of_Bern. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Michael Rieger, Christian Dellenbach, Johannes vom Berg, Jane Beil-
Wagner, Ange Maguy, Stephan Rohr. Enabling comprehensive optogenetic
studies of mouse hearts by simultaneous opto-electrical panoramic
mapping and stimulation. Nature Communications, 2021; 12 (1) DOI:
10.1038/s41467- 021-26039-8 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211005124734.htm

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