title: Non-Ca2+-conducting Ca2+ channels in fish skeletal muscle excitation-contraction coupling.
abstract: During skeletal muscle excitation-contraction (EC) coupling, membrane depolarizations activate the sarcolemmal voltage-gated L-type Ca(2+) channel (Ca(V)1.1). Ca(V)1.1 in turn triggers opening of the sarcoplasmic Ca(2+) release channel (RyR1) via interchannel protein-protein interaction to release Ca(2+) for myofibril contraction. Simultaneously to this EC coupling process, a small and slowly activating Ca(2+) inward current through Ca(V)1.1 is found in mammalian skeletal myotubes. The role of this Ca(2+) influx, which is not immediately required for EC coupling, is still enigmatic. Interestingly, whole-cell patch clamp experiments on freshly dissociated skeletal muscle myotubes from zebrafish larvae revealed the lack of such Ca(2+) currents. We identified two distinct isoforms of the pore-forming Ca(V)1.1alpha(1S) subunit in zebrafish that are differentially expressed in superficial slow and deep fast musculature. Both do not conduct Ca(2+) but merely act as voltage sensors to trigger opening of two likewise tissue-specific isoforms of RyR1. We further show that non-Ca(2+) conductivity of both Ca(V)1.1alpha(1S) isoforms is a common trait of all higher teleosts. This non-Ca(2+) conductivity of Ca(V)1.1 positions teleosts at the most-derived position of an evolutionary trajectory. Though EC coupling in early chordate muscles is activated by the influx of extracellular Ca(2+), it evolved toward Ca(V)1.1-RyR1 protein-protein interaction with a relatively small and slow influx of external Ca(2+) in tetrapods. Finally, the Ca(V)1.1 Ca(2+) influx was completely eliminated in higher teleost fishes.
authors.affiliation: Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Biochemical Pharmacology, Innsbruck Medical University, A-6020 Innsbruck, Austria.
authors.forename: Johann
authors.initials: J
authors.lastname: Schredelseker
authors.forename: Manisha
authors.initials: M
authors.lastname: Shrivastav
authors.forename: Anamika
authors.initials: A
authors.lastname: Dayal
authors.forename: Manfred
authors.initials: M
authors.lastname: Grabner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D056966:Excitation Contraction Coupling; D005399:Fishes / Q000235:genetics / Q000502:physiology*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010802:Phylogeny; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014018:Tissue Distribution; D015027:Zebrafish / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D020746:Calcium Channels, L-Type; D020033:Protein Isoforms; D021122:Protein Subunits; D019837:Ryanodine Receptor Calcium Release Channel; D029961:Zebrafish Proteins