It is well established that cytosolic calcium (Ca2+) acts as a key second messenger in many intracellular pathways including synaptic transmission, muscle contraction, hormonal secretion, cell growth and proliferation. The primary intracellular Ca2+ storage/release organelles in most cells is the endoplasmic reticulum (ER) or the sarcoplasmic reticulum (SR) in striated muscle cells. The ER and SR contain two Ca2+ release channel families, the Inositol trisphosphate receptors (IP3Rs) and the Ryanodine receptors (RyRs). The Ryanodine receptor family consists of three different isoforms: The skeletal muscle isoform, Ryanodine Receptor type 1 (RyR1); the cardiac muscle isoform, Ryanodine Receptor type 2 (RyR2) and the brain isoform, Ryanodine Receptor type 3 (RyR3). The Ryanodine receptors are homotetrameric proteins generating a Ca2+ conducting channel. They play a key role in the mechanism of excitation-contraction coupling in striated muscle. Binding of Ryanodine (poisonous alkaloid found in the South American plant Ryania speciosa to the Ryanodine receptor causes two major changes in the channel: a reduction in single-channel conductance and a marked increase in the open state probability, leading to an overall increase/decrease in the Ca2+ release capability of the channel. RyR3 is the most widely expressed RyR channel which is predominantly expressed in smooth muscle tissues and certain regions of the brain.