Versatile Roles of Intracellularly Located TRPV1 Channel.

The ubiquitous expression in many organs throughout the body and the ability to respond to a wide variety of physical and chemical stimuli have brought transient receptor potential (TRP) channels to the vanguards of our sensory systems. TRP vanilloid-1 (TRPV1) is the founding member of the TRPV subfamily. TRPV1 can be activated by noxious heat, protons, and vanilloids. Previous studies have shown that TRPV1 is located on the plasma membrane, serving to non-selectively permeate calcium ion from the extracellular region to the cytoplasm. Interestingly, increasing evidence suggests that TRPV1 is also located intracellularly in various cell types such as neurons, myocytes, and numerous cancer cells. By immunocytochemistry and/or fractionation followed by Western blotting, TRPV1 was found to express on the endoplasmic reticulum/sarcoplasmic reticulum and the mitochondria. By using various pharmacological and molecular tools, intracellular TRPV1 was also found to functionally express to control calcium level both inside the organelles and in the cytoplasm. Recent studies have shown that intracellularly located TRPV1 serves versatile functions in various physiological and pathological conditions (e.g., exercise endurance and hypertrophy). In this review, we not only have summarized the well-characterized roles of TRPV1, but also have highlighted the increasing importance of intracellular TRPV1-mediated pathways. Lastly, we have pointed out future research direction for answering several important questions that have remained unanswered. Vigorous investigation of the emerging roles of intracellular TRPV1 can allow a better understanding of how TRPV1 controls the cellular calcium homeostasis and its role in various physiological and pathophysiological conditions. J. Cell. Physiol. 232: 1957-1965, 2017. © 2016 Wiley Periodicals, Inc.