Date: 01 Oct 2013

Ryanodine and Inositol Trisphosphate Receptors/Ca2+ Release Channels in Airway Smooth Muscle Cells

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Abstract

Ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs) are the most important Ca2+ release channels on the sarcoplasmic (or endoplasmic) reticulum (SR) in almost all types of cells. In the past several decades, the studies of RyRs and IP3Rs have greatly facilitated our understanding of the physiological functions and pathological mechanisms for various diseases including heart failure, arrhythmias, myopathy, and seizure. Similarly, their important roles have been explored in airway smooth muscle cells (SMCs). These two receptors control intracellular Ca2+ release and modulate extracellular Ca2+ influx, thereby playing an essential role in cell contraction, relaxation, proliferation, migration, metabolism, and, ultimately, cell fate. The abnormality of Ca2+ signaling in airway SMCs may contribute to the development of multiple lung diseases, notably asthma. Concomitantly, many regulators, including Ca2+ itself, calmodulin, protein kinases, FK506-binding protein 12.6 (FKBP12.6), cyclic adenosine diphosphate ribose (cADPR), and redox status, are involved in the regulation of Ca2+ signaling and, thus, the physiological function and pathological alterations. The two SR Ca2+ release channels may also directly or indirectly interact with plasmalemmal and mitochondrial ion channels such as transient receptor potential cation, big-conductance Ca2+-activated K+, Ca2+-activated Cl, and other channels, providing positive or negative feedback mechanisms to control Ca2+ signaling and cellular functions.