Photochemical gating of intracellular Ca2+ release channels

J Am Chem Soc. 2007 May 2;129(17):5316-7. doi: 10.1021/ja069361q. Epub 2007 Apr 11.

Abstract

We have synthesized BiNiX, a caged methylxanthine agonist for the ryanodine receptor (RyR) — the major calcium channel that mediates Ca2+ release from intracellular Ca2+ stores in electrically excitable cells. BiNiX is easily loaded into living cells through incubation with its acetoxymethyl (AM) ester. Delivery of focused UV light pulses to the loaded cell releases paraxanthine focally and rapidly to activate RyRs to release Ca2+, thus elevating intracellular Ca2+ concentration to initiate Ca2+-dependent signaling cascades. We demonstrate the biological utility of BiNiX in heart muscle cells by showing that local intracellular photolysis of BiNiX triggers Ca2+ release and consequent muscle contraction.

Publication types

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

MeSH terms

  • Animals
  • Calcium Channel Agonists / chemical synthesis*
  • Calcium Channel Agonists / pharmacology*
  • Calcium Channels / chemistry*
  • Calcium Signaling / physiology
  • Electrophysiology
  • Ion Channel Gating / physiology*
  • Muscle Cells / drug effects
  • Muscle Cells / metabolism
  • Photochemistry
  • Photolysis
  • Rats
  • Ryanodine Receptor Calcium Release Channel / drug effects
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Sarcoplasmic Reticulum / drug effects
  • Sarcoplasmic Reticulum / metabolism
  • Spectrophotometry, Ultraviolet
  • Xanthines / chemistry

Substances

  • Calcium Channel Agonists
  • Calcium Channels
  • Ryanodine Receptor Calcium Release Channel
  • Xanthines