A single amino acid mutation (G156S) in the putative pore-forming region of
the G protein-sensitive, inwardly rectifying K+ channel subunit, GIRK2, re
nders the conductance constitutively active and nonselective for monovalent
cations. The mutant channel subunit (GIRK2wv) causes the pleiotropic weave
r disease in mice, which is characterized by the selective vulnerability of
cerebellar granule cells and Purkinje cells, as well as dopaminergic neuro
ns in the mesencephalon, to cell death. It has been proposed that divalent
cation permeability through constitutively active GIRK2wv channels contribu
tes to a rise in internal calcium in the GIRK2wv-expressing neurons, eventu
ally leading to cell death. We carried out comparative studies of recombina
nt GIRK2wv channels expressed in Xenopus oocytes and COS-7 cells to determi
ne the magnitude and relative permeability of the GIRK2wv conductance to Ca
2+. Data from these studies demonstrate that the properties of the expresse
d current differ in the two systems and that when recombinant GIRK2wv is ex
pressed in mammalian cells it is impermeable to Ca2+.