Optical mapping of optogenetically shaped cardiac action potentials

Sci Rep. 2014 Aug 19:4:6125. doi: 10.1038/srep06125.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Cells, Cultured
  • Channelrhodopsins
  • Electric Stimulation
  • HEK293 Cells
  • Halorhodopsins / genetics
  • Halorhodopsins / metabolism
  • Humans
  • Light
  • Microelectrodes
  • Microscopy, Confocal
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / physiology*
  • Optogenetics
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Voltage-Sensitive Dye Imaging*

Substances

  • Channelrhodopsins
  • Halorhodopsins