Calcium in ciliated protozoa: sources, regulation, and calcium-regulated cell functions

In ciliates, a variety of processes are regulated by Ca2 � , e.g., exocytosis, endocytosis, ciliary beat, cell contraction, and nuclear migration. Differential microdomain regulation may occur by activation of specific channels in different cell regions (e.g., voltagedependent Ca2 � channels in cilia), by local, nonpropagated activation of subplasmalemmal Ca stores (alveolar sacs), by different sensitivity thresholds, and eventually by interplay with additional second messengers (cilia). During stimulus–secretion coupling, Ca2 � as the only known second messenger operates at �5 �M, whereby mobilization from alveolar sacs is superimposed by ‘‘store-operated Ca2 � influx’ ’ (SOC), to drive exocytotic and endocytotic membrane fusion. (Content discharge requires binding of extracellular Ca2 � to some secretory proteins.) Ca2 � homeostasis is reestablished by binding to cytosolic Ca2�-binding proteins (e.g., calmodulin), by sequestration into mitochondria (perhaps by Ca2 � uniporter) and into endoplasmic reticulum and alveolar sacs (with a SERCA-type pump), and by extrusion via a plasmalemmal Ca2 � pump and a Na � /Ca2 � exchanger. Comparison of free vs total concentration, [Ca2�] vs [Ca], during activation, using time-resolved fluorochrome analysis and X-ray microanalysis, respectively, reveals that altogether activation requires a calcium flux that is orders of magnitude larger than that expected from the [Ca2�] actually required for local activation