Regions of the skeletal muscle dihydropyridine receptor critical for excitation-contraction coupling.
It is thought that in skeletal muscle excitation-contraction (EC) coupling, the release of Ca2+ from the sarcoplasmic reticulum is controlled by the dihydropyridine (DHP) receptor in the transverse tubular membrane, where it serves as the voltage sensor. We have shown previously that injection of an expression plasmid carrying the skeletal muscle DHP receptor complementary DNA restores EC coupling and L-type calcium current that are missing in skeletal muscle myotubes from mutant mice with muscular dysgenesis. This restored coupling resembles normal skeletal muscle EC coupling, which does not require entry of extracellular Ca2+. By contrast, injection into dysgenic myotubes of an expression plasmid carrying the cardiac DHP receptor cDNA produces L-type calcium current and cardiac-type EC coupling, which does require entry of extracellular Ca2+. To identify the regions responsible for this important functional difference between the two structurally similar DHP receptors, we have expressed various chimaeric DHP receptor cDNAs in dysgenic myotubes. The results obtained indicate that the putative cytoplasmic region between repeats II and III of the skeletal muscle DHP receptor is an important determinant of skeletal-type EC coupling.
Tanabe
T
T
Department of Medical Chemistry, Kyoto University Faculty of Medicine, Japan.
Beam
K G
KG
Adams
B A
BA
Niidome
T
T
Numa
S
S
D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D002678:Chimera; D004247:DNA / Q000235:genetics; D004558:Electric Stimulation; D006321:Heart / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008961:Models, Structural; D009119:Muscle Contraction; D009132:Muscles / Q000502:physiology* / Q000503:physiopathology; D010957:Plasmids; D011487:Protein Conformation; D011817:Rabbits; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000502:physiology; D015183:Restriction Mapping; D013779:Tetrodotoxin / Q000494:pharmacology
D015220:Calcium Channels; D011978:Receptors, Nicotinic; D013779:Tetrodotoxin; D004247:DNA