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Ultrastructural studies of the site of action of ryanodine on heart muscle

Summary

A correlation has been identified between the sensitivity of cardiac muscle to ryanodine and the presence in the muscle of a transverse tubular system. Thus ryanodine failed to inhibit cardiac contraction in tissues which lack a transverse tubular system such as mammalian fetal heart and batracian heart. In the mammalian newborn the inhibition of contractile tension by ryanodine increased during that period of growth when evidence for a developing T system was apparent in electron micrographs. Concentrations of ryanodine sufficient to inhibit contraction of adult mammalian heart muscle were observed to alter the ultrastructure of the tissue. Ryanodine treatment brought about a separation of the sarcolemma at the level of the Z lines and appeared to cause wrinkling and an apparent evagination of the sarcolemma at sarcomere lengths of 2 μ or less. It is suggested that ryanodine inhibits contraction of adult mammalian heart muscle by dissociating the T tubules from the sarcoplasmic reticulum system and thus uncoupling excitation from contraction.

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This work was supported by Grant #1104 from the Research Foundation of the City University of New York.

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Penefsky, Z.J. Ultrastructural studies of the site of action of ryanodine on heart muscle. Pflugers Arch. 347, 185–198 (1974). https://doi.org/10.1007/BF00592596

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Key words

  • Structure-Function Relationships
  • Ryanodine
  • Transverse Tubules
  • Excitation-Contraction Coupling