Modulators of intracellular calcium

The importance of calcium in excitation‐contraction coupling in both cardiac and vascular smooth muscle has resulted in an intense research interest into the intracellular regulation of this ion. Selective foci for the modulation of intracellular calcium include the interaction of calcium with the contractile protein apparatus, sites of calcium release and sequestration, and pathways for the extrusion of calcium into the extracellular space. Research efforts directed towards elucidating these phenomena have met with varied degrees of success. The presence of different calcium regulatory systems for contractile protein function, i.e., troponin in cardiac and calmodulin‐myosin light chain kinase in vascular, provides an attractive rationale for the design of selective compounds. The inherent difficulty in studying intracellular release and sequestration presently presently precludes examining the physiological implications of specific inhibition of these phenomena. However, the apparent absence of a sodium‐dependent calcium extrusion pathway in vascular tissue may lead to the design of novel cardiotonics. It is anticipated that further clarification of the similarities and differences in the calcium cycle between these tissues will result in the development of tissue‐selective therapeutic agents.