PKC-SENSITIVE CL- CHANNELS ASSOCIATED WITH CILIARY EPITHELIAL HOMOLOGOF PI(CLN)

Swelling activates and protein kinase C (PKC) downregulates Cl- channe ls in cultured nonpigmented ciliary epithelial (NPE) cells. We now rep ort that the PKC inhibitor staurosporine upregulates whole cell. Cl- c urrents isosmotically. The kinetics and current-voltage relationship a re similar to those of volume-activated Cl- channels of these cells. T hese properties are inconsistent with cloned ClC-0, ClC-1, ClC-2, and MDR1 channels but could reflect the cystic fibrosis transmembrane cond uctance regulator (CFTR) channel or the Cl- channel regulator pI(Cln). CFTR mRNA was undetectable by Northern analysis of cultured NPE cells or ciliary body tissue. In contrast, a human pI(Cln) probe obtained b y polymerase chain reaction cloning and showing 90% identity with the rat cDNA clone detected high levels of transcripts in NPE cells. The l evel was low in tissue, where the NPE message was diluted by RNA from other cells. We conclude that NPE cells display staurosporine-activate d Cl- channels [g(St)(Cl)] likely identical with the volume-activated channels. The same cells expressing gst(Cl) transcribe mRNA for a nove l homologue (pHCBI(Cln)) of pI(Cln) that may regulate Cl- transport in to the aqueous humor.