Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor

Nature. 1996 Mar 7;380(6569):72-5. doi: 10.1038/380072a0.


Excitation-contraction coupling in skeletal muscle involves a voltage sensor in the plasma membrane which, in response to depolarization, causes an intracellular calcium-release channel to open. The skeletal isoform of the ryanodine receptor (RyR-1) functions as the Ca2+-release channel and the dihydropyridine receptor (DHPR) functions as the voltage sensor and also as an L-type Ca2+ channel. Here we examine the possibility that there is a retrograde signal from RyR-1 to the DHPR, using myotubes from mice homozygous for a disrupted RyR-1 gene (dyspedic mice). As expected, we find that there is no excitation-contraction coupling in dyspedic myotubes, but we also find that they have a roughly 30-fold reduction in L-type Ca2+-current density. Injection of dyspedic myotubes with RyR-1 complementary DNA restores excitation-contraction coupling and causes the density of L-type Ca2+ current to rise towards normal. Despite the differences in Ca2+-current magnitude, measurements of charge movement indicate that the density of DHPRs is similar in dyspedic and RyR-1-expressing myotubes. Our results support the possibility of a retrograde signal by which RyR-1 enhances the function of DHPRs as Ca2+ channels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caffeine / pharmacology
  • Calcium / metabolism
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calcium Channels, L-Type
  • Cells, Cultured
  • DNA, Complementary / genetics
  • Gene Targeting
  • Membrane Potentials
  • Mice
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Muscles / drug effects
  • Muscles / metabolism*
  • Rabbits
  • Ryanodine / metabolism*
  • Ryanodine / pharmacology
  • Ryanodine Receptor Calcium Release Channel
  • Signal Transduction


  • Calcium Channels
  • Calcium Channels, L-Type
  • DNA, Complementary
  • Muscle Proteins
  • Ryanodine Receptor Calcium Release Channel
  • Ryanodine
  • Caffeine
  • Calcium