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Canonical Transient Receptor Potential Channel Expression, Regulation, and Function in Vascular and Airway Diseases

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TRP Channels in Drug Discovery

Abstract

The physiological function of all cells is uniquely regulated by changes in cytosolic Ca2+ levels. Although several mechanisms increase cytosolic Ca2+ levels, Ca2+ influx across the plasma membrane upon the release of Ca2+ from the internal stores is one of the major mechanisms in most nonexcitable cells and in some excitable cells. Such Ca2+ channels, which are activated by intracellular Ca2+ store depletion are referred to as store-operated Ca2+ entry (SOCE) channels and have been shown to be essential for many biological functions including fluid and enzyme secretion, immune regulation, hypertension, pulmonary function, neurosecretion, synaptic plasticity, and vascular diseases. Canonical transient receptor potential (TRPCs) have been proposed as components of the store-operated Ca2+ channel (SOCC) which mediates SOCE. TRPC channels are nonselective cation channels, present in a signaling complex where they interact with key proteins critical for their regulation. In this regard, there is increasing recognition that Ca2+ entry via SOCE channels plays critical roles in the lung, particularly for vascular and airway function. Indeed, regulation/targeting of TRPC channels appear to be important in normal vascular and airway physiology as well as pathophysiology of lung diseases. In this chapter, we briefly summarize the current state of knowledge regarding expression, regulation, and function of TRPC channels in the vasculature and the respiratory system.

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Acknowledgments

This work was supported by NIH grants awarded to Brij B Singh (award number RO1 DE 017102-06 and 5P20RR017699), Christina M. Pabelick (R01 HL090595) and Y.S. Prakash (R01 HL088029).

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Singh, B.B., Pabelick, C.M., Prakash, Y.S. (2012). Canonical Transient Receptor Potential Channel Expression, Regulation, and Function in Vascular and Airway Diseases. In: Szallasi, A., Bíró, T. (eds) TRP Channels in Drug Discovery. Methods in Pharmacology and Toxicology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-077-9_4

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