Calcium mobilization via intracellular ion channels, store organization and mitochondria in smooth muscle

Abstract

In smooth muscle, Ca 2+ release from the internal store into the cytoplasm occurs via inositol trisphosphate (IP 3R) and ryanodine receptors (RyR). The internal Ca 2+ stores containing IP 3R and RyR may be arranged as multiple separate compartments with various IP 3R and RyR arrangements, or there may be a single structure containing both receptors. The existence of multiple stores is proposed to explain several physiological responses which include the progression of Ca 2+ waves, graded Ca 2+ release from the store and various local responses and sensitivities. We suggest that, rather than multiple stores, a single luminally-continuous store exists in which Ca 2+ is in free diffusional equilibrium throughout. Regulation of Ca 2+ release via IP 3R and RyR by the local Ca 2+ concentration within the stores explains the apparent existence of multiple stores and physiological processes such as graded Ca 2+ release and Ca 2+ waves. Close positioning of IP 3R on the store with mitochondria or with receptors on the plasma membrane creates ‘IP 3junctions’ to generate local responses on the luminally-continuous store.