GTPγS removal of D-600 block of skeletal muscle excitation-contraction coupling

Lisa Carney-Anderson, Ladora V. Thompson, Daniel A. Huetteman, Sue K. Donaldson

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2 Scopus citations


G proteins interacting with dihydropyridine receptors (DHPR) in transverse tubules (TT) of skeletal muscle may have a role in skeletal excitation-contraction (EC) coupling. The aim of this study was to determine the effects of G protein-specific nucleotides [guanosine 5'-O-(3- thiotriphosphate) (GTPγS) and guanosine 5'-O-(2-thiodiphosphate) (GDPβS)] on the EC coupling mechanism in the presence of D-600, an agent that blocks EC coupling by immobilizing the voltages-sensing subunit of the DHPR in its inactivated state. By use of the mechanically peeled single-fiber preparation from rabbit adductor magnus skeletal muscle, 50 μM GTPγS and 500 μM GDPβS were applied with the fiber in a D-600-induced state of blocked EC coupling. Neither nucleotide served as an independent stimulus for sarcoplasmic reticulum (SR) Ca2+ release when added to the TT polarizing bath under conditions of D-600 block. The presence of GTPγS or GDPβS during a complete EC coupling cycle removed the D-600 block of EC coupling, despite continuous bath D-600. After the nucleotides were washed out, in the continued presence of D-600, the D-600 block of EC coupling was reestablished. In contrast, GTPγS added only during the period of TT depolarization under D-600 block did not remove the D-600 block of EC coupling, even though GTPγS did stimulate SR Ca2+ release. GTPγS had no effect on submaximum (0.5-1.0 mM) caffeine contractures and thus is unlikely to be acting through the Ca2+- induced Ca2+ release mechanism of the SR. These data suggest that the molecular binding site for GTPγS and GDPβS is likely to be in the TT near the DHPR, perhaps on a G protein.

Original languageEnglish (US)
Pages (from-to)C572-C581
JournalAmerican Journal of Physiology - Cell Physiology
Issue number2 41-2
StatePublished - Feb 1997


  • G proteins
  • depolarization-induced tension
  • peeled skeletal muscle fibers
  • sarcoplasmic reticulum calcium release


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