Wireless control of cellular function by activation of a novel protein responsive to electromagnetic fields.

The Kryptopterus bicirrhis (glass catfish) is known to respond to electromagnetic fields (EMF). Here we tested its avoidance behavior in response to static and alternating magnetic fields stimulation. Using expression cloning we identified an electromagnetic perceptive gene (EPG) from the K. bicirrhis encoding a protein that responds to EMF. This EPG gene was cloned and expressed in mammalian cells, neuronal cultures and in rat's brain. Immunohistochemistry showed that the expression of EPG is confined to the mammalian cell membrane. Calcium imaging in mammalian cells and cultured neurons expressing EPG demonstrated that remote activation by EMF significantly increases intracellular calcium concentrations, indicative of cellular excitability. Moreover, wireless magnetic activation of EPG in rat motor cortex induced motor evoked responses of the contralateral forelimb in vivo. Here we report on the development of a new technology for remote, non-invasive modulation of cell function.

Optical Mapping of Ventricular Fibrillation Dynamics.

There is very limited information regarding the dynamic patterns of the electrical activity during ventricular fibrillation (VF) in humans. Most of the data used to generate and test hypotheses regarding the mechanisms of VF come from animal models and computer simulations and the quantification of VF patterns is non-trivial. Many of the experimental recordings of the dynamic spatial patterns of VF have been obtained from mammals using "optical mapping" or "video imaging" technology in which "phase maps" are derived from high-resolution transmembrane recordings from the heart surface. The surface manifestation of the unstable reentrant waves sustaining VF can be identified as "phase singularities" and their number and location provide one measure of VF complexity. After providing a brief history of optical mapping of VF, we compare and contrast a quantitative analysis of VF patterns from the heart surface for four different animal models, hence providing physiological insight into the variety of VF dynamics among species. We found that in all four animal models the action potential duration restitution slope was actually negative during VF and that the spatial dispersion of electrophysiological parameters were not different during the first second of VF compared to pacing immediately before VF initiation. Surprisingly, our results suggest that APD restitution and spatial dispersion may not be essential causes of VF dynamics. Analyses of electrophysiological quantities in the four animal models are consistent with the idea that VF is essentially a two-dimensional phenomenon in small rabbit hearts whose size are near the boundary of the "critical mass" required to sustain VF, while VF in large pig hearts is three-dimensional and exhibits the maximal theoretical phase singularity density, and thus will not terminate spontaneously.

Optical mapping of optogenetically shaped cardiac action potentials.

Light-mediated silencing and stimulation of cardiac excitability, an important complement to electrical stimulation, promises important discoveries and therapies. To date, cardiac optogenetics has been studied with patch-clamp, multielectrode arrays, video microscopy, and an all-optical system measuring calcium transients. The future lies in achieving simultaneous optical acquisition of excitability signals and optogenetic control, both with high spatio-temporal resolution. Here, we make progress by combining optical mapping of action potentials with concurrent activation of channelrhodopsin-2 (ChR2) or halorhodopsin (eNpHR3.0), via an all-optical system applied to monolayers of neonatal rat ventricular myocytes (NRVM). Additionally, we explore the capability of ChR2 and eNpHR3.0 to shape action-potential waveforms, potentially aiding the study of short/long QT syndromes that result from abnormal changes in action potential duration (APD). These results show the promise of an all-optical system to acquire action potentials with precise temporal optogenetics control, achieving a long-sought flexibility beyond the means of conventional electrical stimulation.