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

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.