Developmental and tissue-specific regulation of rabbit skeletal and cardiac muscle calcium channels involved in excitation-contraction coupling.
Two types of calcium channels signal excitation-contraction (E-C) coupling in striated muscle: dihydropyridine receptors (DHPRs, voltage-gated L-type calcium channels on the transverse tubule) and ryanodine receptors (RyRs, calcium release channels on the sarcoplasmic reticulum). Sarcolemmal depolarization activates the DHPR; subsequently, the RyR is activated and releases calcium that activates muscle contraction. We show in the present study that expression of the E-C coupling calcium channels is upregulated during myogenic development in the rabbit. Skeletal and cardiac muscle isoforms of the following genes were examined: the DHPR alpha 1, alpha 2, beta, and gamma subunits and the RyR. Distinct cardiac and skeletal muscle-specific cDNAs were isolated, encoding each of the DHPR subunits and the RyR. The skeletal muscle DHPR alpha 1, alpha 2, beta, and gamma subunits and the cardiac DHPR alpha 1 subunit mRNA levels increased on the day of birth and at the adult stage compared with fetal levels. The skeletal and cardiac RyR mRNA levels increased on the day of birth and at adult stages compared with fetal levels. Ryanodine binding sites increased in both skeletal and cardiac muscle. We now provide a molecular explanation for the physiological "maturation" of the E-C coupling apparatus observed at the day of birth and during early postnatal development in both skeletal and cardiac muscles. Low levels of calcium channel expression in fetal cardiac and skeletal muscle make these tissues more sensitive to pharmacological therapy with calcium channel blockers, a phenomenon that has been reported in human neonates.
Brillantes
A M
AM
Department of Medicine, Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029.
Bezprozvannaya
S
S
Marks
A R
AR
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D015152:Blotting, Northern; D015220:Calcium Channels / Q000096:biosynthesis* / Q000502:physiology; D020746:Calcium Channels, L-Type; D002462:Cell Membrane / Q000378:metabolism; D017931:DNA Primers; D015342:DNA Probes; D018076:DNA, Complementary; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation; D006321:Heart / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009119:Muscle Contraction; D024510:Muscle Development; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000502:physiology; D009132:Muscles / Q000378:metabolism / Q000502:physiology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D016376:Oligonucleotides, Antisense; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*; D011817:Rabbits; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D017931:DNA Primers; D015342:DNA Probes; D018076:DNA, Complementary; D046911:Macromolecular Substances; D009124:Muscle Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine