Genomic and non-genomic action of vitamin D on ion channels – Targeting mitochondria

Abstract

Recent studies revealed that mitochondria are not only a place of vitamin D₃ metabolism but also direct or indirect targets of its activities. This review summarizes current knowledge on the regulation of ion channels from plasma and mitochondrial membranes by the active form of vitamin D₃ (1,25(OH)₂D₃). 1,25(OH)₂D₃, is a naturally occurring hormone with pleiotropic activities; implicated in the modulation of cell differentiation, and proliferation and in the prevention of various diseases, including cancer. Many experimental data indicate that 1,25(OH)₂D₃ deficiency induces ionic remodeling and 1,25(OH)₂D₃ regulates the activity of multiple ion channels. There are two main theories on how 1,25(OH)₂D₃ can modify the function of ion channels. First, describes the involvement of genomic pathways of response to 1,25(OH)₂D₃ in the regulation of the expression of the genes encoding channels, their auxiliary subunits, or additional regulators. Interestingly, intracellular ion channels, like mitochondrial, are encoded by the same genes as plasma membrane channels. Therefore, the comprehensive genomic regulation of the channels from these two different cellular compartments we analyzed using a bioinformatic approach. The second theory explores non-genomic pathways of vitamin D₃ activities. It was shown, that 1,25(OH)₂D₃ indirectly regulates enzymes that impact ion channels, change membrane physical properties, or directly bind to channel proteins. In this article, the involvement of genomic and non-genomic pathways regulated by 1,25(OH)₂D₃ in the modulation of the levels and activity of plasma membrane and mitochondrial ion channels was investigated by an extensive review of the literature and analysis of the transcriptomic data using bioinformatics.