Is ryanodine receptor a calcium or magnesium channel? Roles of K+ and Mg2+ during Ca2+ release

Cell Calcium. 2012 Jun;51(6):427-33. doi: 10.1016/j.ceca.2012.02.001. Epub 2012 Mar 3.


The ryanodine receptor (RyR) is a poorly selective channel that mediates Ca(2+) release from intracellular Ca(2+) stores. How RyR's selectivity between the physiological cations K(+), Mg(2+), and Ca(2+) affects single-channel Ca(2+) current amplitude is examined using a recent model of RyR permeation. It is found that K(+) provides the vast majority of the countercurrent (through RyR itself) that is needed to prevent the sarcoplasmic reticulum (SR) membrane potential from changing and stopping Ca(2+) release. Moreover, intra-pore competition between Ca(2+) and Mg(2+) defines single RyR Ca(2+) current amplitude. Since both [Mg(2+)] and [Ca(2+)](SR) can change during pathophysiological conditions, the RyR unitary Ca(2+) current amplitude during Ca(2+) release may change significantly due to this Ca(2+)/Mg(2+) competition. Compared to the classic action of Mg(2+) on RyR open probability, these Ca(2+) current amplitude changes have as large or larger effects on overall RyR Ca(2+) mobilization. A new aspect of RyR divalent versus monovalent selectivity is also identified where this kind of selectivity decreases as divalent concentration increases.

Publication types

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

MeSH terms

  • Animals
  • Calcium / chemistry*
  • Calcium Channels / chemistry*
  • Cations, Divalent / chemistry
  • Cations, Monovalent / chemistry
  • Cell Membrane Permeability
  • Magnesium / chemistry*
  • Membrane Potentials
  • Muscles / chemistry
  • Potassium / chemistry*
  • Ryanodine Receptor Calcium Release Channel / chemistry*
  • Sarcoplasmic Reticulum / chemistry
  • Thermodynamics


  • Calcium Channels
  • Cations, Divalent
  • Cations, Monovalent
  • Ryanodine Receptor Calcium Release Channel
  • Magnesium
  • Potassium
  • Calcium