Activation of histamine H3 receptor decreased cytoplasmic Ca(2+) imaging during electrical stimulation in the skeletal myotubes.
Histamine is a neurotransmitter and chemical mediator in multiple physiological processes. Histamine H3 receptor is expressed in the nervous system, heart, and gastrointestinal tract; however, little is known about H3 receptor in skeletal muscle. The aim of this study was to investigate the role of H3 receptor in skeletal myotubes. The expression of H3 receptor and myosin heavy chain (MHC), a late myogenesis marker, was assessed by real-time PCR and immunostaining in C2C12 skeletal myogenesis and adult mid-urethral skeletal muscle tissues. H3 receptor mRNA showed a significant increase upon differentiation of C2C12 into myotubes: 1-, 26-, 91-, and 182-fold at days 0, 2, 4, and 6, respectively. H3 receptor immunostaining in differentiated C2C12 cells and adult skeletal muscles was positive and correlated with that of MHC. The functional role of H3receptor in differentiated myotubes was assessed using an H3 receptor agonist, (R)-a-methylhistamine ((R)-α-MeHA). Ca(2+) imaging, stimulated by electric pacing, was decreased by 55% after the treatment of mature C2C12 myotubes with 1μM (R)-α-MeHA for 10min and 20min, while treatment with 100nm (R)-α-MeHA for 5min caused 45% inhibition. These results suggested that H3 receptor may participate in the maintenance of the relaxed state and prevention of over-contraction in mature differentiated myotubes. The elucidation of the role of H3R in skeletal myogenesis and adult skeletal muscle may open a new direction in the treatment of skeletal muscle disorders, such as muscle weakness, atrophy, and myotonia in motion systems or peri-urethral skeletal muscle tissues.
Department of Urology, Institute of Clinic Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 China; Department of Medicine, Helsinki University Central Hospital, Biomedicum 1, PO Box 700, FIN-00029 Helsinki, Finland; Department of Anatomy, University of Helsinki, Biomedicum 1, PO Box 63, FIN-00029 Helsinki, Finland.
Yan
Y
Chen
Unit of Cardiovascular Research, Minerva Foundation Institute for Medical Research, Biomedicum Helsinki 2U, Tukholmankatu 8, 00290, Helsinki, Finland.
Jere
J
Paavola
Department of Medicine, Helsinki University Central Hospital, Biomedicum 1, PO Box 700, FIN-00029 Helsinki, Finland; Department of Anatomy, University of Helsinki, Biomedicum 1, PO Box 63, FIN-00029 Helsinki, Finland.
Vasili
V
Stegajev
Goethe University, Institute of Pharmaceutical Chemistry, ZAFES/OSF/NeFF, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany.
Holger
H
Stark
School of Biological & Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, Durham, UK.
Paul L
PL
Chazot
Department of Urology, Institute of Clinic Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 China. Electronic address: wenjg@hotmail.com.
Jian Guo
JG
Wen
Department of Medicine, Helsinki University Central Hospital, Biomedicum 1, PO Box 700, FIN-00029 Helsinki, Finland; ORTON Orthopedic Hospital of the ORTON Foundation, Tenholantie 10, 00280 Helsinki, Finland; COXA Hospital for Joint Replacement, Biokatu 6 B, 33520 Tampere, Finland. Electronic address: yrjokonttinen@sina.com.
Yrjö T
YT
Konttinen
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D017442:Histamine Agonists / Q000494:pharmacology*; D008761:Methylhistamines / Q000494:pharmacology; D051379:Mice; D008856:Microscopy, Fluorescence; D024510:Muscle Development / Q000187:drug effects / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000096:biosynthesis / Q000502:physiology*
D017442:Histamine Agonists; D008761:Methylhistamines; D018100:Receptors, Histamine H3; C069357:alpha-methylhistamine; D018995:Myosin Heavy Chains; D002118:Calcium
Calcium; Electrical stimulation; Histamine H(3) receptor; Skeletal myogenesis; Skeletal myotubes