In higher organisms, the situation is less clear. Ca2+ uptake usually occurs via a thapsigargin-insensitive pathway (therefore precluding SERCA involvement) and appears to be dependent upon the H+ gradient; whether this occurs via a single (unknown) CHX or via exchangers in series (e.g. Na+/H+ exchanger coupled to a Na+/Ca2+ exchanger) is unproven. Acidic vesicles in some cell types may well take a leaf out of the yeasts'/plants' book and host two uptake pathways, but whether this is a widespread template is unclear.