Dysregulation of Neurogenic Calcium Signaling and Autism

The calcium ion is one of the most versatile biological signaling molecules, known to regulate physiological systems at every level from membrane potential and ion transporters to kinases, transcription factors, and even cell morphology. It is also one of the most universal and ancient of cellular signals. A diverse host of diseases, importantly including a number of rare syndromes that include a phenotype on the autism spectrum (ASD), are coming to be recognized to be caused by disruptions of intracellular calcium homeostasis, and an emerging pathophysiological mechanism of disease, a calciumopathy, is at its formative stage (Stutzmann et al. 2006; Bezprozvanny and Gargus 2008). Calcium passively enters the cytoplasm across the plasma membrane and is cleared from the cytoplasm to a level far below extracellular levels by a host of calcium pumps and carriers at the expense of metabolic energy. It is eliminated back out across the plasma membrane but is also, importantly, sequestered for subsequent rapid release within intracellular storage sites which include the endoplasmic reticulum (ER) and the mitochondria. Cytosolic calcium signals originate either by the rapid release of intracellular stores through intracellular ion channels or by extracellular calcium entering