Calcium il' Ciliated Protozoa: Sources, Regulation, and Calcium-Regulated Cell Functions

In ciliates, a variety of processes are regulated by Ca', 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 Ca' 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, Ca' as the only known second messenger operates at -5 f.tM, whereby mobilization from alveolar sacs is superimposed by "store-operated Ca+influx" (SaC), to drive exocytotic and endocytotic membrane fusion. (Content discharge requires binding of extracellular Ca2+ to some secretory proteins.) Ca+ homeostasis is reestablished by binding to cytosolic Ca+-binding proteins (e.g., calmodulin), by sequestration into mitochondria (perhaps by Ca+ 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, [Ca+] 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 [Ca+] actually required for local activation.