Frontiers 2021

In recent years, scientists have found ways to control cells using light. This field, known as optogenetics, uses special proteins called channelrhodopsins (ChRs)—light-sensitive molecules originally found in algae. When introduced into heart cells, these proteins allow us to influence the electrical activity of the heart with a flash of light.

This technology holds great promise for studying and even treating heart conditions. But with many different ChR variants available, and each with its own quirks, we need to understand how they behave—especially in a diseased heart or after repeated use. That’s exactly what we set out to explore in this study.

What Did We Do?

We worked with heart muscle cells from newborn rats, called neonatal rat ventricular myocytes (NRVMs). Some of these cells were made "sick" by treating them with a chemical that causes them to mimic a diseased, enlarged heart—this is known as pathological hypertrophy.

We tested four different ChR variants in both healthy and diseased cells:

• H134R – a common and fast-acting ChR.

• CatCh – a variant with higher calcium flow and sensitivity.

• ReaChR – activated by red light, useful for deeper tissues.

• GtACR1 – an anion channel that works differently from the others.

We used light pulses of different colors and durations to activate these ChRs and measured how well they worked. We looked at:

• The electrical current they generated in cells.

• How quickly they activated and deactivated.

• How repeated light exposure affected their performance.

• Whether diseased cells responded differently than healthy ones.

To simulate real use, we also tested how the ChRs responded to being activated over and over again—mimicking what would happen during prolonged pacing or arrhythmia treatments.

Why Is This Important?

If optogenetics is to be used for real-world heart therapies or advanced research, we need to ensure it works reliably, even under stress. That means:

• ChRs must function in diseased hearts, not just healthy ones.

• They must withstand repeated use—just like a defibrillator might need to be used more than once in a crisis.

• Their behavior needs to be predictable, so that scientists and doctors can pick the right tool for the job.

Our study fills a big knowledge gap by showing, for the first time, how different ChRs behave in heart cells that are both healthy and hypertrophied, and how their performance holds up under repetitive use.

Key Findings

1. All ChR Variants Work in Diseased Cells

We found that all four ChRs performed just as well in the “diseased” hypertrophied cells as they did in healthy ones. This is great news—it means pathological remodeling of the heart doesn’t impair the basic function of these optogenetic tools.

2. Each ChR Has a Unique Signature

Each variant behaved differently when hit with light. For instance:

• GtACR1 produced the strongest currents but had a milder effect on membrane voltage.

• CatCh gave large currents and strong depolarization.

• H134R was the fastest, which could be useful for precise timing.

• ReaChR, although slower, responded to red light and may be better for deeper tissues.

These differences can be seen in the Figure, where we show how the membrane voltage changes after light exposure in each case.

Journal info

Article type:  Research article
Impact factor: 4.755
ISSN: 1664042X