Christian S Wright1,2, Alexander G Robling2,3, Mary C Farach-Carson4, William R Thompson5,6,7. 1. Department of Physical Therapy, School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, IN, 46202, USA. 2. Indiana Center for Musculoskeletal Health, Indiana University, Indianapolis, IN, 46202, USA. 3. Department of Anatomy & Cell Biology, Indiana University, Indianapolis, IN, 46202, USA. 4. Department of Diagnostic & Biomedical Sciences, University of Texas Health Science Center at Houston School of Dentistry, Houston, TX, 77054, USA. 5. Department of Physical Therapy, School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, IN, 46202, USA. thompwil@iu.edu. 6. Indiana Center for Musculoskeletal Health, Indiana University, Indianapolis, IN, 46202, USA. thompwil@iu.edu. 7. Department of Anatomy & Cell Biology, Indiana University, Indianapolis, IN, 46202, USA. thompwil@iu.edu.
Abstract
Voltage-sensitive calcium channels (VSCCs) are ubiquitous multimeric protein complexes that are necessary for the regulation of numerous physiological processes. VSCCs regulate calcium influx and various intracellular processes including muscle contraction, neurotransmission, hormone secretion, and gene transcription, with function specificity defined by the channel's subunits and tissue location. The functions of VSCCs in bone are often overlooked since bone is not considered an electrically excitable tissue. However, skeletal homeostasis and adaptation relies heavily on VSCCs. Inhibition or deletion of VSCCs decreases osteogenesis, impairs skeletal structure, and impedes anabolic responses to mechanical loading. RECENT FINDINGS: While the functions of VSCCs in osteoclasts are less clear, VSCCs have distinct but complementary functions in osteoblasts and osteocytes. PURPOSE OF REVIEW: This review details the structure, function, and nomenclature of VSCCs, followed by a comprehensive description of the known functions of VSCCs in bone cells and their regulation of bone development, bone formation, and mechanotransduction.
Voltage-sensitive calcium channels (VSCCs) are ubiquitous multimeric protein complexes that are necessary for the regulation of numerous physiological processes. VSCCs regulate calcium influx and various intracellular processes including muscle contraction, neurotransmission, hormone secretion, and gene transcription, with function specificity defined by the channel's subunits and tissue location. The functions of VSCCs in bone are often overlooked since bone is not considered an electrically excitable tissue. However, skeletal homeostasis and adaptation relies heavily on VSCCs. Inhibition or deletion of VSCCs decreases osteogenesis, impairs skeletal structure, and impedes anabolic responses to mechanical loading. RECENT FINDINGS: While the functions of VSCCs in osteoclasts are less clear, VSCCs have distinct but complementary functions in osteoblasts and osteocytes. PURPOSE OF REVIEW: This review details the structure, function, and nomenclature of VSCCs, followed by a comprehensive description of the known functions of VSCCs in bone cells and their regulation of bone development, bone formation, and mechanotransduction.
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