CLONING AND CHARACTERIZATION OF A NOVEL BK CHANNEL ISOFORM HIGHLY EXPRESSED IN GLIOMA CELLS

摘要

Described is the cloning and functional characterization of a novel splice variant of hSlo, the gene encoding the alpha-subunit of IbTX sensitive human BK channels. The novel isoform of BK channels, which was termed gBK, contains a 63 amino acid insert at splice site 2, which differs by 33 amino acids from its nearest relative hbr5. gBK channels were over-expressed in glioma cells as evident from examination of human biopsy specimens. Moreover, gBK channel expression correlated positively with the relative degrees of malignancy of the tumor tissues. Heterologous expression of gBK in oocytes revealed that the pharmacological and biophysical properties of gBK are consistent with the properties of native BK currents in glioma cells. Furthermore, even when compared with its most homologous form hbr5, gBK showed distinct properties, including slowed channel activation and importantly, enhanced Ca2+ sensitivity at physiologically relevant [Ca2+]i values.