Altered inhibition of the rat skeletal ryanodine receptor/calcium release channel by magnesium in the presence of ATP

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Abstract

Magnesium-induced inhibition of the skeletal ryanodine receptor/calcium-release channel (RyR) was studied in the presence and absence of ATP under isolated conditions and in situ, by examining the RyR incorporated into a planar lipid bilayer and the calcium release flux (Rre1) in isolated single fibres mounted in the double Vaseline gap system. When the incorporated RyR had been activated by calcium (50 μM) in the absence of ATP, the magnesium-induced inhibition showed cooperativity with a Hill coefficient (N) of 1.83 and a half-inhibitory concentration (IC50) of 635 μM. When the open probability was measured in the presence of 5 mM ATP and at a low calcium concentration, the magnesium-induced inhibition was non-cooperative (N=1.1, IC50=860 μM). In isolated muscle fibres, in the presence of ATP, lowering the intracellular magnesium concentration ([Mg2+]i) increased the maximal Rre1 and shifted its voltage dependence to more negative membrane potentials. Increasing [Mg2+]i had the opposite effect. The concentration dependence was described with an IC50 of 174 μM, N=1, under depolarized conditions and showed a tenfold increase in affinity in polarized fibres. At the concentration required for the measurements from isolated fibres, ATP had a full activatory effect on the isolated channel. At a low calcium concentration, the RyR had two ATP-binding sites with half-activatory concentrations of 19 and 350 μM, respectively.

Original languageEnglish
Pages (from-to)729-738
Number of pages10
JournalPflugers Archiv European Journal of Physiology
Volume441
Issue number6
DOIs
Publication statusPublished - Mar 14 2001

Keywords

  • ATP
  • Calcium release
  • Magnesium
  • Ryanodine receptor
  • Skeletal muscle

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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