VCU news

By Frances Dumenci

Researchers from Virginia Commonwealth University have unveiled a new technique to show how a form of oxygen modifies “pacemaker channels” that contribute to memory, heart rate, pain sensation and other functions. The study was published in the current issue of The Journal of General Physiology.

The molecular oxygen in the air, which we breathe every day and is essential for most forms of life, typically stays at a lower energy, relatively stable state. Under certain circumstances, such as in skin cells under sunlight, the molecular oxygen can receive energy and transform into singlet oxygen.

Singlet oxygen is very reactive and modifies proteins, DNA and lipids. Small amounts of singlet oxygen produced during metabolic reactions can also act as a local signaling factor that oxidizes and modifies target molecules, but the underlying mechanisms are poorly understood.

Lei Zhou, Ph.D., assistant professor in the Department of Physiology and Biophysics in the VCU School of Medicine, and his colleagues are using a new technique to explore how singlet oxygen modifies target molecules. This technique provides new insights about singlet oxygen and sets the stage for a better understanding of the highly reactive and challenging substance.

“A molecular understanding of how singlet oxygen works has been missing, largely due to its volatile chemical nature. This study, for the first time, provides a peek into the modification of proteins by singlet oxygen at a molecular level, which in the long term should benefit several health-related areas,” Zhou said.

Previous research has shown that singlet oxygen generated by an outside source, such as through a photochemical reaction, could modify ion channels anchored on the cell membrane. However in those studies, long light exposure in terms of seconds or minutes was required.

By tagging the HCN channel with a fluorescent photosensitizer and applying millisecond laser light pulses, Zhou and his research team were able to elicit the production of small amounts of singlet oxygen in a precise location and monitor its effects on the channels in open and closed states.

HCN channels are referred to as “pacemaker channels” because they help to generate rhythmic activity within heart and brain cells. The current flowing through HCN channels plays a key role in the control of cardiac and neuronal rhythm.

The study’s results indicate that some of the singlet oxygen effects on HCN channels are state specific, whether they are open or closed, and involve specific modifications near the activation gate. Furthermore, the study sheds light on the still mysterious instantaneous current conducted by HCN channels and its implications to physiological functions, including pacemaking, learning and memory, and pain sensation.

The findings not only help explain how singlet oxygen functions, they introduce a method that can be used to further explore this important signaling factor and the potential of singlet oxygen as a biophotonics tool.