title: The mammalian skeletal muscle DHPR has larger Ca2+conductance and is phylogenetically ancient to the early ray-finned fish sterlet (Acipenser ruthenus).
abstract: The L-type Ca2+channel or dihydropyridine receptor (DHPR) in vertebrate skeletal muscle is responsible for sensing sarcolemmal depolarizations and transducing this signal to the sarcoplasmic Ca2+release channel RyR1 via conformational coupling to initiate muscle contraction. During this excitation-contraction (EC) coupling process there is a slow Ca2+current through the mammalian DHPR which is fully missing in euteleost fishes. In contrast to ancestral evolutionary stages where skeletal muscle EC coupling is still depended on Ca2+-induced Ca2+-release (CICR), it is possible that the DHPR Ca2+conductivity during mammalian (conformational) EC coupling was retained as an evolutionary remnant (vestigiality). Here, we wanted to test the hypothesis that due to the lack of evolutionary pressure in post-CICR species skeletal muscle DHPR Ca2+conductivity gradually reduced as evolution progressed. Interestingly, we identified that the DHPR of the early ray-finned fish sterlet (Acipenser ruthenus) is phylogenetically positioned above the mammalian rabbit DHPR which retained robust Ca2+conductivity, but below the euteleost zebrafish DHPR which completely lost Ca2+conductivity. Remarkably, our results revealed that sterlet DHPR still retained the Ca2+conductivity but currents are significantly reduced compared to rabbit. This decrease is due to lower DHPR membrane expression similar to zebrafish, as well as due to reduced channel open probability (Po). In both these fish species the lower DHPR expression density is partially compensated by higher efficacy of DHPR-RyR1 coupling. The complete loss of Poin zebrafish and other euteleost species was presumably based on the teleost specific 3rd round of genome duplication (Ts3R). Ts3R headed into the appearance of two skeletal muscle DHPR isoforms which finally, together with the radiation of the euteleost clade, fully lost the Po.
authors: Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Biochemical Pharmacology, Medical University of Innsbruck, Peter Mayr Strasse 1, A-6020, Innsbruck, Austria.
authors: Kai
authors: K
authors: Schrötter
authors: Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Biochemical Pharmacology, Medical University of Innsbruck, Peter Mayr Strasse 1, A-6020, Innsbruck, Austria.
authors: Anamika
authors: A
authors: Dayal
authors: Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Biochemical Pharmacology, Medical University of Innsbruck, Peter Mayr Strasse 1, A-6020, Innsbruck, Austria. Electronic address: manfred.grabner@i-med.ac.at.
authors: Manfred
authors: M
authors: Grabner
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002478:Cells, Cultured; D005399:Fishes; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D010802:Phylogeny; D011817:Rabbits; D015027:Zebrafish
chemical_list: D020746:Calcium Channels, L-Type; D002118:Calcium
keywords: Calcium influx evolution; Excitation-contraction coupling; L-Type calcium channel; Skeletal muscle; Sterlet DHPR