CALCIUM-ACTIVATED CHLORIDE CONDUCTANCE IS NOT INCREASED IN PANCREATICDUCT CELLS OF CF MICE

Calcium-activated anion secretion is elevated in the pancreatic ductal epithelium of transgenic cf/cf mice which lack the cystic fibrosis tr ansmembrane conductance regulator (CFTR). To elucidate whether this ef fect is due to increased activity of calcium-activated chloride channe ls, we have studied the relationship between CFTR and calcium-activate d chloride currents in pancreatic duct cells isolated from Cambridge c f/cf mice. CFTR chloride currents activated by cAMP were detected in 5 9% (29/49) of wild-type cells and in 50% (20/40) of heterozygous cells . However, we could not detect any CFTR currents in the homozygous cf/ cf cells (0/25). The maximum CFTR current density measured at a membra ne potential of 60 mV was 23.5 +/- 2.8 pA/pF (n = 29) in wild-type cel ls, and about half that value, i.e. 12.4+/-1.6 pA/pF (n = 20) in heter ozygotes (P = 0.004). Calcium-activated chloride currents were detecte d in 73% (24/33) of wild-type, 75% (21/28) of heterozygous and in 58% (7/12) of homozygous cf/cf cells. There was no significant difference between the steady-state calcium-activated current densities in the th ree genotypic groups; the current measured at 60 mV being 527 +/- 162 pA/pF (n = 24) from wild-type, 316+/-35 pA/pF (n = 21) from heterozygo te and 419+/-83 pA/pF (n = 7) from homozygous cells. Our data suggest that lack of CFTR does not enhance the calcium-activated chloride cond uctance in murine pancreatic duct cells.